How Diabetes Causes Kidney Disease – Each kidney is made up of millions of tiny filters called nephrons. Over time, high blood sugar from diabetes can damage blood vessels in the kidneys as well as nephrons so they don’t work as well as they should. Many people with diabetes also develop high blood pressure, which can damage kidneys too.
Is chronic renal failure caused by diabetes?
Diabetes is the leading cause of kidney failure, accounting for 44% percent of new cases. Current research suggests that control of high blood pressure is a key factor in slowing this disease. Strict control of blood sugar levels and reduction of dietary protein intake are also important. Treatment to prevent diabetic kidney disease should begin early — before kidney damage develops.
In the United States, over 29 million people have diabetes. Of these, 21.0 million are diagnosed and 8.1 million are undiagnosed. In 2013, diabetes led to more than 51,000 new cases of kidney failure and over 247,000 people are currently living with kidney failure resulting from diabetes. Diabetes is characterized by high levels of blood sugar, resulting from insufficient production of insulin or defects in insulin action in the body. Type 2 diabetes (also called noninsulin-dependent diabetes) is far more common than type 1 (insulin-dependent diabetes), accounting for about 90 to 95 percent of the cases of diabetes. Type 2 diabetes is most common in people over 40, but is increasing among younger people including children and adolescents. Diabetes damages small blood vessels throughout the body, affecting the kidneys as well as other organs and tissues including skin, nerves, muscles, intestines and the heart. Patients with diabetes can develop high blood pressure as well as rapid hardening of the arteries, which can also lead to heart disease and eye disorders. Diabetes is more prevalent in certain ethnic groups. In American adults aged 20 or older, diabetes has been diagnosed in 13.2% of non-Hispanic blacks, 12.8% of Hispanics, 9% of Asian Americans and 7.6% of non-Hispanic whites. The risk factors for type 1 diabetes include autoimmune, genetic and environmental factors. Risk factors for type 2 diabetes include older age, obesity, family history of diabetes, prior history of gestational diabetes (diabetes during pregnancy), impaired glucose tolerance, physical inactivity and race or ethnicity. Research suggests high blood pressure may be the most important predictor for diabetics developing chronic kidney disease. Specific high blood pressure medications such as angiotensin converting enzyme (ACE) inhibitors and the angiotensin-2 receptor blockers (ARBs) may be the most effective in preventing diabetic kidney disease. It is important for diabetics to keep their blood pressure lower than 130/80. Some of the signs that diabetics may be developing chronic kidney disease include protein in the urine, high blood pressure, leg swelling or cramps, increased need to urinate (especially at night), abnormal blood tests (glomerular filtration rate, GFR), less need for insulin or anti-diabetic pills, nausea and vomiting, weakness, pallor and anemia, itching and diabetic eye disease. Treatment for diabetic kidney disease includes controlling blood pressure and blood sugar levels, reducing dietary protein intake, avoiding medications that may damage the kidneys, treating urinary tract infections and exercise and weight loss (under the supervision of a physician). More than 35% of people aged 20 years or older with diabetes have chronic kidney disease. If current trends continue, it is estimated that 1 in 3 U.S. adults will have diabetes in the year 2050 compared to 1 in 10 today.
Updated January 2016 Sources of Facts and Statistics: United States Renal Data System, Centers for Disease Control and Prevention, National Institute of Diabetes and Digestive and Kidney Diseases, National Diabetes Education Program
How does diabetic nephropathy lead to CKD?
Diabetic nephropathy causes – Diabetic nephropathy is a common complication of type 1 and type 2 diabetes. Over time, poorly controlled diabetes can cause damage to blood vessel clusters in your kidneys that filter waste from your blood. This can lead to kidney damage and cause high blood pressure.
Why does type 2 diabetes cause kidney failure?
How does diabetes cause kidney disease? – High blood glucose, also called blood sugar, can damage the blood vessels in your kidneys. When the blood vessels are damaged, they don’t work as well. Many people with diabetes also develop high blood pressure, which can also damage your kidneys. Learn more about high blood pressure and kidney disease,
Why does GFR decrease in diabetes?
Discussion – Glucose lowering therapy correlated with a lowering of the GFR. This was observed from the fact that the GFR levels on admission were high and above the normal range (157.4; >80–130ml/min) and they decreased to levels in the normal range (86.4ml/min) Additionally random blood sugar levels were also high on admission (hyperglycemic) and were lowered to normal at discharge. This implies that glucose lowering therapy or glycaemic control has an effect of lowering GFR. These findings are similar to Christiansen’s and Schmitz’s findings that GFR decreased after short term treatment. Physiologically, high glucose levels are known to cause hyperfiltration (GFR above normal) of the kidney. Since the glucose levels were lowered, the kidney’s function of filtering materials goes back to the normal rate. Results from this study are similar to the findings by Rudy 2003 and Mongensen 2004 who found that glycaemic control reduces hyperfiltration and hence having an effect of lowering the GFR. In terms of sex, GFR decreased both in males and females although the decrease in males was not statistically significant. This could partly be explained by Wishner’s findings that complications of DM have a significant impact on women (Wishner 1996:47). The GFR at discharge lies in the normal range but it tends towards the lower normal. This could be attributed to the duration at which these patients had stayed with diabetes mellitus since the longer the patient stays with the disease, the worse their renal function gets. Since GFR is the most reliable estimate of the amount of residual kidney function as mentioned by Alexander 2007, the results of this study imply that control of blood glucose removed the hyperfiltration which is reflected in the reduction in GFR. The value of GFR at discharge was in the normal range implying repaired renal function of diabetes mellitus patients improved after short term admission for hyperglycemia treatment.
What are the three leading causes of CKD?
Diabetes. High blood pressure. Heart (cardiovascular) disease. Smoking.
Why does creatinine increase in diabetes?
Healthy kidneys, which have powerful filtering units in them, trap the creatinine and eliminate most of it in urine. Diabetes can damage the filtering system and reduce the ability to clean waste from your blood, so creatinine accumulates in your circulation.
Does diabetes reduce GFR?
DISCUSSION – Long-standing type 1 diabetic patients with normal AER are still at risk of developing clinically significant nephropathy (16,17). It is therefore important to identify markers of increased nephropathy risk among these patients. One possibility is to perform kidney biopsies in such patients, given that those with more advanced glomerulopathy are more likely to develop abnormalities in AER (7).
However, this is not very practical in most clinical settings. Thus, we examined whether reduced GFR can be predictive of more advanced underlying glomerular lesions. We previously reported that reduced GFR in eight normoalbuminuric long-standing type 1 diabetic women was associated with worse diabetic glomerular lesions (5).
Shortly thereafter, a small group of normoalbuminuric long-standing type 1 and type 2 diabetic largely female patients with reduced GFR was described (6). A similar prevalence of reduced GFR was reported among long-standing normoalbuminuric and normotensive type 1 diabetic patients in Brazil (18).
Reduced GFR has also been observed in normoalbuminuric type 2 diabetic patients in Denmark (19), but the higher prevalence of hypertension among type 2 diabetic patients could have accounted for some GFR loss. However, other investigators (20) did not encounter reduced GFR in normoalbuminuric type 1 diabetic patients.
Based on this paucity of information and these conflicting results, the present study was undertaken using a much larger cohort of patients and confirmed that reduced GFR occurs among normoalbuminuric long-standing type 1 diabetic patients. This, and the earlier studies (5,6), showed a marked predominance of this phenomenon in women.
Our earlier report (5) suggested that, at least in part, the sex effect could be related to the self-selection of a low protein diet among female patients, but this was not investigated in the present cohort. As noted, a large cross-sectional study did not observe reduced GFR among normoalbuminuric type 1 diabetic patients (20).
However, diabetes duration was shorter (20), mean of 14 years in this study versus 23 years in the present study. Also, patients with diabetes duration as brief as 1 year were included in the former (20) versus a minimum of 10 years in the present study.
- Moreover, only 29% of the patients in the study of Hansen et al.
- 20) were women as compared with 62% in the current study.
- Finally, patients on antihypertensive drugs were excluded from this earlier study (20), whereas our report indicates that low GFR is much more common among normoalbuminuric patients who are on these medications.
Thus, the differences in the findings of the present and the earlier report of Hansen et al. (20) are best explained by the marked differences in inclusion criteria and patient demographics. These differences are unlikely to be explained by differences in GFR methodology.
- Although inulin clearance is considered to be the gold standard for GFR estimates, iothalamate clearances are highly correlated with the inulin method (21).
- Creatinine clearances with home urine collections are generally considered to provide a less precise estimate of true GFR, at least in part due to collection inaccuracies.
However, as already described, multiple supervised clinical research center creatinine clearances are highly correlated with inulin clearances (11) and show no deviation or trend in Bland-Altman analysis. Moreover, 96% of the low GFR group had creatinine clearance measurements.
- There were very strong correlations between this GFR estimate and renal structure within this group, further supporting the validity of this carefully performed measure as an indicator of underlying renal pathology.
- Although some still question this point (3), this study confirms that normoalbuminuric type 1 diabetic patients have increased Vv(Mes/glom) in addition to Vv(MM/glom) and GBM width and decreased Sv(PGBM/glom).
Moreover, the presence of low GFR was associated with worse diabetic glomerular lesions. The statistical differences between the low GFR and the normal GFR normoalbuminuric groups were maintained when patients on antihypertensive medications were excluded from the analyses.
- This excludes the possibility that our findings were caused by patient misclassification, i.e., the inclusion of patients who would be microalbuminuric if not on antihypertensive drugs, or by grouping errors secondary to GFR having been reduced by these drugs.
- A relatively high proportion of patients, hypertensive by current standards, was not receiving antihypertensive treatment, and only a small number of patients were on ACE inhibitors.
This is because many of these patients were studied when the definition of hypertension was different (22) and when ACE inhibitors were not available or commonly used. Studies evaluating structural-functional relations in diabetic nephropathy among patients ranging from normoalbuminuria to proteinuria demonstrate that AER, blood pressure, and GFR are strongly correlated with glomerular structure (13,23,24).
Thus, patients with worse lesions also have clinical changes of increased AER and blood pressure and reduced GFR. The present study in long-standing normoalbuminuric type 1 diabetic patients confirms the association between GFR and glomerular structural parameters, even in patients with normal AER. Usually, diabetic patients developing diabetic nephropathy will initially present with increased AER followed by or concomitant with increased blood pressure before GFR decline occurs.
However, as confirmed here, a significant fraction of patients do not follow this pattern, as they can have reduced GFR and increased blood pressure before AER increases. Other efforts are being undertaken to identify normoalbuminuric patients at increased diabetic nephropathy risk before microalbuminuria or proteinuria develops.
- Thus, Lurbe et al.
- 4) recently reported that nighttime ambulatory blood pressure values and “nondipper” status were significant predictors of progression from normoalbuminuria to microalbuminuria in adolescent patients with type 1 diabetes.
- In addition, we agree with the general thesis of the editorial by Ingelfinger (25) accompanying the article of Lurbe et al.
(4), which argues that it is important to identify the subset of normoalbuminuric patients at increased nephropathy risk, perhaps as candidates for improved glycemic control and other therapies. Because it would not be practical to perform renal biopsies in all normoalbuminuric patients, we recommend that long-standing normoalbuminuric type 1 diabetic female patients with retinopathy or hypertension should have GFR measured on a regular basis.
As the risk of low GFR in similarly defined men is just over 10%, this recommendation should be considered for men in terms of cost-to-benefit ratio. The importance of identifying such low GFR patients is based on the observation that long-standing normoalbuminuric patients who progress to diabetic nephropathy have worse baseline diabetic glomerular lesions than those remaining normoalbuminuric (7).
Similarly, glomerular structure in microalbuminuric type 1 diabetic patients was a predictor of AER after 6 years of follow-up (26). Also, in a cohort of type 1 diabetic adolescents in transition from normoalbuminuria to microalbuminuria, the rate of GFR decline (although still within the normal range) was correlated with GBM width (27).
- It should be appreciated that the severity of the glomerular structural lesions in the normoalbuminuric patients with low GFR presented here was similar to that of microalbuminuric type 1 diabetic patients with similar diabetes duration (data not presented).
- Considering these findings, it is not surprising that ∼10% of long-standing normoalbuminuric type 1 diabetic patients will progress to diabetic nephropathy (16,17,28,29).
Taken together, these studies show a wide range of lesions in normoalbuminuric long-standing diabetic patients and suggest that the severity of these lesions is predictive of progression to microalbuminuria and overt nephropathy (7,27). The diabetic patients recruited into the studies presented here may not be representative of the entire population of long-standing normoalbuminuric type 1 diabetic patients.
However, there is no reason to believe that other patients with the characteristics of the low GFR group, i.e., diabetes duration 10–40 years, female sex, and presence of retinopathy, hypertension, or both, would be different from those in this report. For this reason and those reasons argued above, we recommend that such patients have annual GFR measurements.
In the final analysis, however, the true value of this recommendation will only be disclosed by longitudinal studies. TABLE 1 Demographic and clinical characteristics in long-standing normoalbuminuric type 1 diabetic patients
| Normal GFR group | Low GFR group | P | |
|---|---|---|---|
| n | 82 | 23 | |
| Sex (male/female) | 36/46 | 4/19 | 0.021 |
| Age (years) | 35.2 ± 9.5 | 36.0 ± 8.0 | NS |
| Age at diabetes onset (years) | 12.9 ± 7.0 | 11.3 ± 7.9 | NS |
| Diabetes duration (years) | 22.2 ± 9.6 | 24.6 ± 8.0 | NS |
| HbA 1c (%) | 8.5 ± 1.6 | 8.4 ± 1.1 | NS |
| Serum creatinine (mg/dl) * | 0.84 ± 0.17 | 0.96 ± 0.21 | 0.005 |
| SBP (mmHg) | 119.8 ± 10.9 | 116.8 ± 12.9 | NS |
| DBP (mmHg) | 71.2 ± 7.8 | 71.7 ± 7.3 | NS |
| MBP (mmHg) | 87.6 ± 8.2 | 86.5 ± 8.4 | NS |
| Hypertension (yes/no) | 27/55 | 11/12 | NS |
| Antihypertensive treatment (yes/no) | 13/69 | 9/14 | 0.022 |
| ACEI or AIIRB (yes/no) | 4/78 | 3/20 | NS |
| GFR (ml · min −1 · 1.73 m −2 ) † | 121.2 ± 16.6 | 75.9 ± 11.7 | ND |
| AER (μg/min) | 7.7 (2.8–19.9) | 7.7 (2.0–17.6) | NS |
| Retinopathy (none/background/proliferative) | 33/31/15 | 2/11/10 | 0.006 |
table>
Data are means ± SD, n, and median (range). ACEI, ACE inhibitor; AIIRB, angiotensin II type 1 receptor blocker; DBP, diastolic blood pressure; MBP, mean blood pressure; SBP, systolic blood pressure. * To convert values to μmoles/l, multiply by 88.4; † to convert values to ml/s, multiply by 0.01667.
| Control | Normal GFR | Low GFR | P | |
|---|---|---|---|---|
| GBM width (nm) | 331.5 ± 45.7 | 469.4 ± 84.2 | 544.5 ± 140.7 | <0.001 |
| Vv(Mes/glom) | 0.20 ± 0.03 | 0.28 ± 0.06 | 0.34 ± 0.08 | <0.001 |
| Vv(MM/glom) | 0.09 ± 0.02 | 0.15 ± 0.04 | 0.20 ± 0.06 | <0.001 |
| Vv(MC/glom) | 0.08 ± 0.02 | 0.08 ± 0.02 | 0.10 ± 0.02 | <0.001 |
| Sv(PGBM/glom) (μm 2 /μm 3 ) | 0.126 ± 0.018 | 0.116 ± 0.019 | 0.094 ± 0.021 | <0.001 |
table>
How does insulin affect GFR?
Abstract – Background: Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. Methods: We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of hippuran, iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. Results: During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. Conclusions: Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.
What are the two 2 most common causes of CKD?
About Chronic Kidney Disease – CKD is a condition in which the kidneys are damaged and cannot filter blood as well as they should. Because of this, excess fluid and waste from blood remain in the body and may cause other health problems, such as heart disease and stroke. More than 1 in 7 15% of US adults are estimated to have chronic kidney disease, that is about 37 million people. Some other health consequences of CKD include:
Anemia or low number of red blood cells Increased occurrence of infections Low calcium levels, high potassium levels, and high phosphorus levels in the blood Loss of appetite or eating less Depression or lower quality of life
CKD has varying levels of seriousness. It usually gets worse over time though treatment has been shown to slow progression. If left untreated, CKD can progress to kidney failure and early cardiovascular disease. When the kidneys stop working, dialysis or kidney transplant is needed for survival.
Kidney diseases are a leading cause of death in the United States. About 37 million US adults are estimated to have CKD, and most are undiagnosed. 40% of people with severely reduced kidney function (not on dialysis) are not aware of having CKD. Every 24 hours, 360 people begin dialysis treatment for kidney failure. In the United States, diabetes and high blood pressure are the leading causes of kidney failure, accounting for 3 out of 4 new cases, In 2019, treating Medicare beneficiaries with CKD cost $87.2 billion, and treating people with ESRD cost an additional $37.3 billion,
What is the pathophysiology of CKD?
Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia, nocturia, lassitude, fatigue, pruritus, decreased mental acuity, muscle twitches and cramps, water retention, undernutrition, peripheral neuropathies, and seizures.
Diagnosis is based on laboratory testing of renal function, sometimes followed by renal biopsy. Treatment is primarily directed at the underlying condition but includes fluid and electrolyte management, blood pressure control, treatment of anemia, various types of dialysis, and kidney transplantation.
The most common causes in the US in order of prevalence are Chronic kidney disease (CKD) is initially described as diminished renal reserve or renal insufficiency, which may progress to renal failure (end-stage renal disease). Initially, as renal tissue loses function, there are few noticeable abnormalities because the remaining tissue increases its performance (renal functional adaptation). Decreased renal function interferes with the kidneys’ ability to maintain fluid and electrolyte homeostasis. The ability to concentrate urine declines early and is followed by decreases in ability to excrete excess phosphate, acid, and potassium. When renal failure is advanced (glomerular filtration rate ≤ 15 mL/min/1.73 m 2 ), the ability to effectively dilute or concentrate urine is lost; thus, urine osmolality is usually fixed at about 300 to 320 mOsm/kg, close to that of plasma (275 to 295 mOsm/kg), and urinary volume does not respond readily to variations in water intake. Plasma concentrations of creatinine and urea (which are highly dependent on glomerular filtration) begin a hyperbolic rise as GFR diminishes. These changes are minimal early on. When the GFR falls below 15 mL/min/1.73 m 2 (normal > 90 mL/min/1.73 m 2 ), creatinine and urea levels are high and are usually associated with systemic manifestations (uremia). Urea and creatinine are not major contributors to the uremic symptoms; they are markers for many other substances (some not yet well-defined) that cause the symptoms. For substances whose secretion is controlled mainly through distal nephron secretion (eg, potassium), renal adaptation usually maintains plasma levels at normal until renal failure is advanced or dietary potassium intake is excessive. Potassium-sparing diuretics Diuretics A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers. read more, angiotensin-converting enzyme inhibitors Angiotensin-converting enzyme (ACE) inhibitors A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers. read more, beta-blockers Beta-blockers A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers. read more, nonsteroidal anti-inflammatory drugs, Nonopioid Analgesics Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or. read more cyclosporine, tacrolimus, trimethoprim /sulfamethoxazole, pentamidine, or angiotensin II receptor blockers Angiotensin II receptor blockers (ARBs) A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers. read more may raise plasma potassium levels in patients with less advanced renal failure. Abnormalities of calcium, phosphate, parathyroid hormone (PTH), and vitamin D metabolism Vitamin D Deficiency and Dependency Inadequate exposure to sunlight predisposes to vitamin D deficiency. Deficiency impairs bone mineralization, causing rickets in children and osteomalacia in adults and possibly contributing. read more can occur, as can renal osteodystrophy. Decreased renal production of calcitriol (1,25(OH) 2 D, the active vitamin D hormone) contributes to hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4. read more, Decreased renal excretion of phosphate results in hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical. read more, Secondary hyperparathyroidism is common and can develop in renal failure before abnormalities in calcium or phosphate concentrations occur. For this reason, monitoring PTH in patients with moderate CKD, even before hyperphosphatemia occurs, has been recommended. Renal osteodystrophy (abnormal bone mineralization resulting from hyperparathyroidism, calcitriol deficiency, elevated serum phosphate, or low or normal serum calcium) usually takes the form of increased bone turnover due to hyperparathyroid bone disease (osteitis fibrosa) but can also involve decreased bone turnover due to adynamic bone disease (with increased parathyroid suppression) or osteomalacia. Calcitriol deficiency may cause osteopenia or osteomalacia. Anemia is characteristic of moderate to advanced CKD ( ≥ stage 3). The anemia of CKD is normochromic-normocytic, with a hematocrit of 20 to 30% (35 to 40% in patients with polycystic kidney disease Autosomal Dominant Polycystic Kidney Disease (ADPKD) Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. Almost all forms are. read more ). It is usually caused by deficient erythropoietin production due to a reduction of functional renal mass (see page Anemias Caused by Deficient Erythropoiesis Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction.
read more ). Other causes include deficiencies of iron Iron Deficiency Iron (Fe) is a component of hemoglobin, myoglobin, and many enzymes in the body. Heme iron is contained mainly in animal products. It is absorbed much better than nonheme iron (eg, in plants. read more, folate Folate Deficiency Folate deficiency is common.
It may result from inadequate intake, malabsorption, or use of various drugs. Deficiency causes megaloblastic anemia (indistinguishable from that due to vitamin. read more, and vitamin B12 Vitamin B12 Deficiency Dietary vitamin B12 deficiency usually results from inadequate absorption, but deficiency can develop in vegans who do not take vitamin supplements.
What is the mechanism leading to CKD?
Abstract – It is estimated that over 10% of the adult population in developed countries have some degree of chronic kidney disease (CKD). CKD is a progressive and irreversible deterioration of the renal excretory function that results in implementation of renal replacement therapy in the form of dialysis or renal transplant, which may also lead to death.
- CKD poses a growing problem to society as the incidence of the disease increases at an annual rate of 8%, and consumes up to 2% of the global health expenditure.
- CKD is caused by a variety of factors including diabetes, hypertension, infection, reduced blood supply to the kidneys, obstruction of the urinary tract and genetic alterations.
The nephropathies associated with some of these conditions have been modeled in animals, this being crucial to understanding their pathophysiological mechanism and assessing prospective treatments at the preclinical level. This article reviews and updates the pathophysiological knowledge acquired primarily from experimental models and human studies of CKD.
It also highlights the common mechanism(s) underlying the most relevant chronic nephropathies which lead to the appearance of a progressive, common renal phenotype regardless of aetiology. Based on this knowledge, a therapeutic horizon for the treatment of CKD is described. Present therapy primarily based upon renin-angiotensin inhibition, future diagnostics and therapeutic perspectives based upon anti-inflammatory, anti-fibrotic and hemodynamic approaches, new drugs targeting specific signaling pathways, and advances in gene and cell therapies, are all elaborated.2010 Elsevier Inc.
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Is high creatinine related to diabetes?
Discussion – Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl even after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. The highest category of serum creatinine levels (serum creatinine ≥1.10 mg/dl) was significantly associated with an increased risk of T2DM in women; however, this association disappeared after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. The results for men with creatinine below 1.20 mg/dl in our study were consistent with those of previous studies in Japanese men. A study including 31,343 Japanese men without diabetes with a median observation of 7.7 years showed that low cumulative average serum creatinine levels were associated with an increased risk of diabetes after adjusting for age, smoking, BMI, hypertension, and dyslipidemia, Among 8570 Japanese men aged 40–55 years at entry who had fasting plasma glucose levels < 126 mg/dl and serum creatinine levels < 2.0 mg/dl during the 4-year follow-up period, low serum creatinine was associated with an increased risk of T2DM, Because we did not exclude those with comorbidities such as cardiovascular disease or cancer at baseline or those older than 65 years, other confounding factors may affect the results regarding the association between serum creatinine levels and the risk of T2DM in men with serum creatinine above 1.2 mg/dl. Our study showed that although there was a trend that reduced levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, the association between the level of serum creatinine and the risk of incident diabetes was not significant in women. However, there were several studies showing that the inverse association between the level of serum creatinine and the risk of incident diabetes was consistent for both sexes. In a previous study including 9667 Japanese individuals without diabetes or hypertension and with normal creatinine levels at baseline during the follow-up period (mean: 5.6 years), low serum creatinine levels independently predicted T2DM development in both men and women, A Chinese cohort study including 41,439 participants (44.5% of those were women) who were ≥ 18 years (range 18–96) and did not have T2DM found that low serum creatinine levels were associated with an increased risk of T2DM after the exclusion of cardiovascular disease, cancer, and abnormally high serum creatinine levels (> 1.2 mg/dL for men and > 1.0 for women) for both men and women, Because we included women with mildly elevated levels of serum creatinine (1.0–1.4 mg/dl) and did not exclude those with comorbidities such as hypertension, cardiovascular disease, or cancer, other confounding factors affecting serum creatinine may influence the results regarding the association between serum creatinine levels and the risk of incident diabetes in women. The results regarding the association between the levels of serum creatinine and the risk of incident diabetes were different between men and women in our study. Additionally, a previous study in Korean subjects demonstrated that serum creatinine was more closely associated with the risk of T2DM in men than in women, Because total muscle mass is known to be different by sex, the difference in muscle mass may affect the different results regarding the association between serum creatinine levels and the risk of T2DM between men and women. Women were reported to have lower skeletal muscle mass than men. The mean value of serum creatinine was reported to be higher in men than in women in a previous study, The mechanism of the association between serum creatinine levels and the risk of incident diabetes is not clear. Several studies have demonstrated the close association between low muscle mass and dysglycemia. Among Korean subjects aged 65 or older, IR was higher in the obese group with relatively low muscle mass than in the obese group without low muscle mass, Additionally, hyperinsulinemia, a compensatory response to maintain plasma glucose levels within normal ranges as an early predictor of IR, was significantly associated with loss of skeletal muscle mass in a cohort study of individuals without diabetes at the 4.6-year follow-up, Increased muscle mass was associated with reduced IR and a decreased risk of diabetes, The improvement of the amount of lean mass with nutritional supplements was associated with increased insulin sensitivity in elderly subjects with low muscle mass, Insulin receptors in the muscle are known to play a key role in the regulation of glucose metabolism. Because skeletal muscle is the major site of insulin-mediated glucose uptake in the postprandial phase, the defect of skeletal muscle IR was suggested be the pathogenesis of the development of type 2 diabetes, Increased total lean mass was associated with a decreased risk of incident diabetes for older normal-weight women, Since myokines released by muscle fibers were reported to have systemic effects on the liver, adipose tissue, and pancreas function, lack of myokines such as interleukin-6 and myostatin due to reduced muscle mass may influence IR, Additionally, insulin sensitizer medication use (metformin and/or thiazolidinediones) may attenuate muscle loss in men with impaired fasting glucose and diabetes, Because insulin is a potent anabolic stimulus for skeletal muscle, it is possible that defects in insulin signaling can induce a reduction in muscle synthesis, Additionally, glomerular hyperfiltration observed early in the natural history in patients with diabetes could contribute to the association between low serum creatinine and the risk of incident diabetes mellitus. Although we did not measure the amount of ectopic adipose tissue such as visceral or epicardial adipose tissue, ectopic accumulation of adipose tissue combined with low muscle mass would affect the association between the levels of serum creatinine and the risk of incident diabetes. Further studies are needed to clarify the mechanism between the close association between serum creatinine levels and the incidence of T2DM. Our study has several strengths. We used a larger data cohort than a previous study in the Korean population. Because the participants were recruited for health checkups at the national scale, it is reasonable to generalize the results of our study in Korea. Additionally, as women have less muscle mass than men, we analyzed subjects by sex separately. There were some limitations. Although the measurement of serum creatinine was reliable, serum creatinine was measured in different laboratories in Korea. We did not measure the indices of IR such as homeostasis model assessment of IR due to lack of data of insulin or C-peptide. Also we did not measure sarcopenic obesity related pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor which could lead IR. Furthermore, we did not evaluate the dietary habits or physical activity that might confound the association between the levels of serum creatinine and the risk of incident diabetes. Other confounding factors, such as family history of diabetes or comorbidities that might affect the amount of muscle mass and the development of incident diabetes, were not adjusted for. Furthermore, we used serum creatinine at baseline only, and we cannot assess the relationship between the change in serum creatinine and the risk of diabetes during the follow-up period. Because our study is an observational study, it was difficult to clarify the mechanism of the relationship between serum creatinine and incident diabetes. We did not classify diabetes as type 1 or type 2 diabetes because we did not check β-cell function or islet cell autoantibodies. Asian individuals have more fat with less skeletal muscle than other ethnic groups, including European and Pacific Island adults, Furthermore, the risk of diabetes tended to be higher among Asian participants than among Caucasian subjects for the same categories of BMI, Ethnic differences in body composition may contribute to the differences in the association between serum creatinine and the risk of incident diabetes, and it is difficult to generalize the results of our study in other ethnicities.
Is creatinine level related to diabetes?
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Epidemiology / Health Services Research | March 01 2009 Nobuko Harita, MD ; 1 Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan Search for other works by this author on: Tomoshige Hayashi, MD, PHD ; Tomoshige Hayashi, MD, PHD 1 Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan Search for other works by this author on: Kyoko Kogawa Sato, MD, PHD ; Kyoko Kogawa Sato, MD, PHD 1 Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan Search for other works by this author on: Yoshiko Nakamura, MD, PHD ; Yoshiko Nakamura, MD, PHD 2 Kansai Health Administration Center, Nippon Telegraph and Telephone West Corporation, Osaka, Japan Search for other works by this author on: Takeshi Yoneda, MD ; 1 Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan Search for other works by this author on: Ginji Endo, MD, PHD ; 1 Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan Search for other works by this author on: Hiroshi Kambe, MD 1 Department of Preventive Medicine and Environmental Health, Osaka City University Graduate School of Medicine, Osaka, Japan 2 Kansai Health Administration Center, Nippon Telegraph and Telephone West Corporation, Osaka, Japan Search for other works by this author on: Diabetes Care 2009;32(3):424–426 OBJECTIVE —Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes.
- RESEARCH DESIGN AND METHODS —The study participants were nondiabetic Japanese men ( n = 8,570) aged 40–55 years at entry.
- Type 2 diabetes was diagnosed if fasting plasma glucose was ≥126 mg/dl or if participants were taking oral hypoglycemic medication or insulin.
- RESULTS —During the 4-year follow-up period, 877 men developed type 2 diabetes.
Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44–2.54) compared with those who had levels between 0.71 and 0.80 mg/dl.
CONCLUSIONS —Lower serum creatinine increased the risk of type 2 diabetes. Although skeletal muscle is one of the major target organs of insulin (1–3), to our knowledge, no prospective study has investigated the association between total skeletal muscle mass and type 2 diabetes. Serum creatinine is primarily a metabolite of creatine, almost all of which is located in skeletal muscle.
Because the amount of creatine per unit of skeletal muscle mass is consistent and the breakdown rate of creatine is also consistent, plasma creatinine concentration is very stable and a direct reflection of skeletal muscle mass (4). If skeletal muscle mass is associated with type 2 diabetes, consequently, serum creatinine might also be associated with type 2 diabetes.
How does insulin affect creatinine?
Abstract – In order to investigate the relationship between insulin response to oral glucose load and renal function, a 100-gm. oral glucose tolerance test was performed in twenty-two patients with chronic glomerulonephritis, whose creatinine clearances ranged form 5 to 96 ml.
per minute. Glucose areas during oral glucose load were little affected by the creatinine clearance in this study. Insulin area during oral glucose load increased in proportion to the decrease in creatinine clearance. The ratio of insulin area to glucose area correlated closely with creatinine clearance and a linear relationship was obtained (y = 1.46 – 0.01x, r = -0.82, p less than 0.001).
There were also significant correlations with serum creatinine, blood urea nitrogen, and PSP (r = 0.6, 0.63, and -0.62, respectively). These results show that the impaired renal function has a significant influence on the plasma insulin levels, and it seems likely that such influence becomes manifest below approximately 60 ml.
What is the most common cause of chronic renal failure?
About Chronic Kidney Disease – CKD is a condition in which the kidneys are damaged and cannot filter blood as well as they should. Because of this, excess fluid and waste from blood remain in the body and may cause other health problems, such as heart disease and stroke. More than 1 in 7 15% of US adults are estimated to have chronic kidney disease, that is about 37 million people. Some other health consequences of CKD include:
Anemia or low number of red blood cells Increased occurrence of infections Low calcium levels, high potassium levels, and high phosphorus levels in the blood Loss of appetite or eating less Depression or lower quality of life
CKD has varying levels of seriousness. It usually gets worse over time though treatment has been shown to slow progression. If left untreated, CKD can progress to kidney failure and early cardiovascular disease. When the kidneys stop working, dialysis or kidney transplant is needed for survival.
Kidney diseases are a leading cause of death in the United States. About 37 million US adults are estimated to have CKD, and most are undiagnosed. 40% of people with severely reduced kidney function (not on dialysis) are not aware of having CKD. Every 24 hours, 360 people begin dialysis treatment for kidney failure. In the United States, diabetes and high blood pressure are the leading causes of kidney failure, accounting for 3 out of 4 new cases, In 2019, treating Medicare beneficiaries with CKD cost $87.2 billion, and treating people with ESRD cost an additional $37.3 billion,
Is diabetic kidney disease the same as chronic kidney disease?
Microvascular changes within the kidney often lead to chronic kidney disease (CKD), an entity referred to as diabetic kidney disease (DKD) or diabetic nephropathy 6.
Can you have kidney failure without having diabetes?
Chronic Kidney Disease a Warning Sign Independent of Hypertension or Diabetes | Johns Hopkins Bloomberg School of Public Health Two new studies from the and the Chronic Kidney Disease Prognosis Consortium found that the presence of chronic kidney disease itself can be a strong indicator of the risk of death and end-stage renal disease (ESRD) even in patients without hypertension or diabetes.
- Both hypertension and diabetes are common conditions with chronic kidney disease with hypertension being the most prevalent.
- The studies were released online in advance of publication in The Lancet,
- Chronic kidney disease affects 10 to 16 percent of all adults in Asia, Europe, Australia and the United States.
Kidney function is measured by estimating glomerular filtration rate and kidney damage is often quantified by measuring albumin, the major protein in the urine standardized for urine concentration. In the hypertension meta-analysis, low kidney function and high urine protein was associated with all-cause and cardiovascular mortality and ESRD in both individuals with and without hypertension.
- The associations of kidney function and urine protein with mortality outcomes were stronger in individuals without hypertension than in those with hypertension, whereas the kidney function and urine protein associations with ESRD did not differ by hypertensive status.
- In the diabetes analysis, individuals with diabetes had a higher risk of all-cause, cardiovascular mortality and ESRD compared to those without diabetes across the range of kidney function and urine protein.
Despite their higher risks, the relative risks of these outcomes by kidney function and urine protein are much the same irrespective of the presence or absence of diabetes. “Chronic kidney disease should be regarded as at least an equally relevant risk factor for mortality and ESRD in individuals without hypertension as it is in those with hypertension,” said Bakhtawar K.
Mahmoodi, MD, PhD, lead author of the hypertension analyses. “These data provide support for clinical practice guidelines which stage chronic kidney disease based on kidney function and urine protein across all causes of kidney disease. The conclusions are strengthened by the findings of leading studies and the participation of investigators from 40, countries and a detailed analysis of over 1 million participants,” said, the Consortium’s principal investigator and professor in the Bloomberg School’s,
“Association of kidney disease measures with mortality and end-stage renal disease in individuals with and without hypertension: a meta-analysis” (lead author, Bakhtawar K. Mahmoodi, MD, PhD, from the Johns Hopkins Bloomberg School of Public Health and University Medical Center Groningen, the Netherlands) and “Association of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis” (lead author Caroline Fox, MD, from the Framingham Heart Study) were written by the Chronic Kidney Disease Prognosis Consortium (CKD-PC), which includes approximately 200 collaborators and data from 40 countries.
What is diabetic renal failure?
Diabetic kidney disease is a decrease in kidney function that occurs in some people who have diabetes. It means that your kidneys are not doing their job as well as they once did to remove waste products and excess fluid from your body. These wastes can build up in your body and cause damage to other organs.