Kidney Disease

Introduction:

Kidneys are the organs that help filter waste products from the blood. They are also involved in regulating blood pressure, electrolyte balance, and red blood cell production in the body. When kidneys fail, harmful wastes build up in the body, blood pressure may rise, and the body may retain excess fluid. Kidney disease may reduce red blood cell production resulting in anemia. Several conditions discussed below may lead to kidney failure. Methods used to prevent or control these conditions will therefore prevent kidney disease or worsening of kidney disease.

 

Risks of kidney disease:

Patients with any type of acute or chronic kidney disease is associated with a higher mortality rate than those without kidney disease (1).

 

Signs of kidney disease:

A patient with the following conditions should be evaluated for kidney disease: signs of low urine production, increasing blood pressure, fluid retention, edema, difficulty in emptying the bladder, reduction of flow, painful urination, discolored urine, bloody urine, fatigue, weight loss, new seizure, or flank pain. Asymptomatic kidney disease, (either acute or chronic) is sometimes detected incidentally on metabolic panel, radiology imaging, or urinalysis.

 

Evaluation for kidney disease:

Any signs of kidney disease should prompt further evaluation with a comprehensive metabolic panel, urinalysis, urine electrolytes, urine protein, urine for eosinophils, urine microalbumin, urine sediment, and renal ultrasound. Further evaluation will be determined by the physician.Without the signs and symptoms above, adults over age 25 and should have a minimum yearly comprehensive metabolic panel to monitor for developing chronic kidney disease without symptoms followed by more frequent checks if needed as recommended by the physician.

 

Diagnosis of kidney disease:

Acute kidney injury, formally known as acute renal failure, is diagnosed once it meets the following criteria: The 3 major criteria used to determine presence of acute kidney injury is as follows (2). (Further criteria used to stage more severe acute kidney injury will not be discussed here.)

• Risk, Injury, and Failure, Loss, and End-stage kidney disease criteria (RIFLE): Increase in creatinine over 50% within 7 days or less.
• Kidney Disease/Improving Global Outcomes criteria (KDIGO): Increase in creatinine by 0.3 mg/dL in 48 hours or over 50% within 7 days or less.
• Acute Kidney Injury Network criteria (AKIN): Increase in creatinine by 0.3 mg/dL or over 50% within 48 hours or less.

 

Chronic kidney disease is diagnosed once the following criteria are met (3):

Over 3 months with a glomerular filtration rate of under 60 ml/min per 1.73 m2, over 3 months of elevated urine albumin or over 3 months of radiographic kidney abnormalities according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) in 2002 and endorsed by the Kidney Disease, Improving Global Outcomes (KDIGO) in 2004.

 

Established diagnosis of kidney disease:

Referral to a Nephrologist is necessary to optimize renal function by treatment, to reduce morbidity, and to reduce risk of mortality.

 

Conditions which may cause chronic kidney disease:

Diabetes and kidney disease (Diabetic nephropathy):

Diabetes mellitus is the most common cause of kidney disease. Taking lifestyle measures to prevent, control or reverse diabetes by strictly controlling blood glucose will, in turn, prevent kidney disease or reduce progression of kidney disease. See the diabetes mellitus section in Preventive Health Advisor.

The earliest sign of kidney disease in diabetics is the presence of microalbuminuria (protein seen in the urine). The American Diabetic Association recommends to provide annual screening to all type 2 diabetes mellitus patients for microalbuminuria starting at the time of diagnosis and for type 1 diabetes mellitus, starting 5 years after diagnosis (4). Compliance to this recommendation was reported to be suboptimal at times among primary care physicians, but electronic medical records and quality control has improved adherence (5). Patients should be educated about this necessity to reinforce their own self compliance. Taking lifestyle measures to treat diabetes by strictly controlling blood glucose will, in turn, reduce diabetic nephropathy rate of progression. Medications called angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARB’s) may prevent or in some cases, reverse rate of kidney disease progression (6). These medications reduce proteinuria.

 

Hypertension related kidney disease:

Hypertension may not only lead to cardiovascular disease, but also it is the most common cause of kidney disease after diabetes mellitus. The key to preventing hypertension related complications is to diagnose hypertension early and treat it before it has been present long enough to cause chronic disease. Hypertension may be discovered years after it starts but treating hypertension even if found late will prevent progression of kidney disease.

 

Medication affect upon the kidneys:

Avoid contrast and nephrotoxic drugs whenever possible.

 

Contrast:

Avoid contrast with CT scans and MRI scans when it is not necessary to use it, or is not likely to add any important diagnostic information. Patients should discuss with the ordering physician about whether contrast is necessary. In patients without fluid restriction, hydrate well prior to a procedure which uses contrast to improve renal clearance of contrast. Before a procedure, MRI or CT scan, increase hydration over the 24 hours prior until urine is maintained as clear without any tint of yellow, then before the procedure, the patient should drink 1 liter per hour for 2 hours. Avoid contrast in diabetics taking metformin within 48 hours which may lead to a complication of lactic acidosis.

 

Non-steroidal anti-inflammatory drugs:

Patients should avoid frequent or long term use of non-steroidal anti-inflammatory drugs which may cause interstitial nephritis, membranous glomerular nephropathy and minimal change renal disease (7).

 

Obstruction and kidney disease:

Prostate disease such as benign prostatic hyperplasia, prostate cancer or kidney stones may lead to renal failure if obstruction is not promptly relieved. For these conditions, referral to Urology is often necessary to relieve the obstruction.

 

Blood vessel diseases of the kidneys:

Aneurysms, malformations, renal artery stenosis, and peripheral vascular disease in the arteries supplying the kidneys may result in renal failure. The majority of these diseases are caused by atherosclerosis. Western style diet, sedentary lifestyle, smoking, diabetes, uncontrolled high blood pressure, and hyperlipidemia may result in atherosclerosis. Good lifestyle choices will prevent atherosclerosis to a significant degree.

 

Pre-renal failure:

Conditions related to low blood volume or low perfusion states such as heart failure, liver disease, dehydration, blood loss, and diarrhea may result in renal failure. Treatment of the underlying cause is indicated. Dehydration should be avoided at all times by drinking adequate water unless fluid restriction is necessary for heart failure or other conditions. For severe dehydration such as in heat illness, or infectious diarrhea, a rehydration regimen with 4-8 ounces of water alternating with the same amount of Gatorade or Pedialyte may be consumed every 5-10 minutes with use of a timer if necessary over the course of 2 hours. This regimen allows rehydration promptly while reducing nausea which often accompanies illness. If oral fluid intake is not possible in setting of severe dehydration, intravenous fluids are required.

 

Chronic kidney disease Integrative Medicine options:

Chronic kidney disease, hypertension, and pycnogenol:

Pycnogenol, French maritime pine bark extract, may be helpful to those suffering from metabolic syndrome. Study participants (n=58) were split into two groups. Both groups were being treated with Ramipril (5mg twice daily), an anti-hypertensive medication, and were instructed to follow a healthier lifestyle. One group was given Pycnogenol (50 mg 3 times/day) in addition to ramipril. Results show that Pycnogenol plus Ramipril significantly further lowered blood pressure (BP) when compared to the group taking Ramipril alone. After 6 months of treatment, average BP in the Ramipril group was lowered to an almost high value of 128.2/90.2 mmHg, while the value in the group taking Pycnogenol with Ramipril reached near normal levels (122.2/85.3 mmHg). Kidney function improved in both groups. With Ramipril alone, urinary protein decreased by 22% but with the addition of Pycnogenol it decreased by 52.7%.  The group taking Pycnogenol also had a lowered fasting blood glucose level, which was reduced from high values to healthy values after 6 months of treatment. Only the group taking Pycnogenol was found to significantly lost weight after 6 months from average BMI 26.5 to 25.0. (8)

Researchers reported the benefits of adding Pycnogenol, French maritime pine bark extract, to a standard medical treatment of hypertensive (high blood pressure) patients with deteriorating kidney function. The participants (n=55) were randomly assigned to receive either Pycnogenol plus the blood pressure-lowering drug ramipril (ACE inhibitor) or ramipril (10 mg) alone for 6 months. Urinary albumin was used as a measure of kidney function – albumin is the most abundant protein in people with kidney problems which leaks from the kidney into the urine. The authors found that albumin levels in the urine decreased significantly in the Pycnogenol group (-52 mg/day) compared to ramipril alone (-23 mg/day only). Pycnogenol also improved systolic and diastolic flow by 12% and 8%, respectively. (9)

 

Chronic kidney disease and coenzyme Q10:

Twenty-one individuals with chronic renal (kidney) failure either on or off dialysis were randomized to receive coenzyme Q10 (CoQ10) at 60 mg, 3 times daily (n=11) or placebo (n=10) for 4 weeks. At the end of the study period, significantly less participants were on dialysis in the CoQ10 group (36.2%) than in the placebo group (90.0%).There was also a significant reduction in levels of creatinine and blood urea and a significant increase in creatinine clearance and urine output in the CoQ10 group, indicating an increase in kidney function, versus the placebo group. (10)

 

Kidney disease and comparison of phosphate binders:

In a systematic review, Navaneethan SD et al evaluated 40 trials for the various effects of phosphate binders in patients with chronic kidney disease. In patients with chronic kidney disease, treatment with calcium salts (calcium acetate and calcium carbonate) resulted in a significantly lower phosphorus level (often elevated due to kidney disease) and parathyroid hormone levels (regulate calcium and phosphate levels) compared to patients taking sevelamer, a drug commonly used to treat high blood levels of phosphorus in patients with kidney disease. However, sevelamer was found to lower the risk of elevated calcium levels by 53% compared to calcium salts. Patients taking sevelamer were also 39% more likely to experience gastro-intestinal side-effects than those taking calcium salts. The authors determined that a lack of research exists regarding how phosphate binders affect morbidity and mortality of patients. (11)

 

Progression of Kidney Disease and Dietary Protein Intake

Reducing or eliminating red meat may reduce the risk of worsening kidney disease. Lew QJ et al (11) studied different sources of protein within the diets of over 63,000 Chinese adults age 45 to 74. The intake of red meat, fish, eggs, poultry, and dairy product intake was obtained by a food questionnaire. Researchers found that 951 cases of end-stage renal disease (ESRD), the kind of kidney disease that requires hemodialysis, occurred over a 15 1/2 years. It was found that the risk of end-stage renal disease increased as as the amount of red meat intake increased. Additionally, substituting red meat with another protein source was found to reduce the risk of ESRD.

 

Assessment and Plan:

• Acute or chronic kidney disease is associated with a higher mortality rate than those without kidney disease (1).

 

• Any signs of kidney disease should prompt further evaluation with a comprehensive metabolic panel, urinalysis, urine electrolytes, urine protein, urine for eosinophils, urine microalbumin, urine sediment, and renal ultrasound. Further evaluation will be determined by the physician. Without the signs and symptoms above, adults over age 25 and should have a minimum yearly comprehensive metabolic panel to monitor for developing chronic kidney disease without symptoms followed by more frequent checks if needed as recommended by the physician.

 

• Depending on which criteria used, diagnosis of acute kidney injury includes:
  • Increase in creatinine of over 50% within 7 days or less, or
  • Increase in creatinine of 0.3 mg/dL in 48 hours, or
  • Increase in creatinine of over 50% within 7 days or less, or
  • Simply increase in creatinine by 0.3 mg/dL, or
  • Increase in creatinine of over 50% within 48 hours or less

 

• Chronic kidney disease is diagnosed by (3):
  • Glomerular filtration rate of under 60 ml/min per 1.73 m2 over 3 months, or
  • Elevated urine albumin for 3 months, or
  • Radiographic kidney abnormalities for 3 months

 

• Referral to a Nephrologist is necessary to optimize renal function by treatment, to reduce morbidity, and to reduce risk of mortality.

 

• Diabetes mellitus is the most common cause of kidney disease, and lifestyle measures to prevent, control or reverse diabetes will, in turn, prevent kidney disease or reduce progression of kidney disease. See the diabetes mellitus section in Preventive Health Advisor.

 

• The American Diabetic Association recommends to provide annual screening to all type 2 diabetes mellitus patients for microalbuminuria starting at the time of diagnosis and for type 1 diabetes mellitus, starting 5 years after diagnosis (4). Patients should be educated about this necessity to reinforce their own self compliance.

 

• Taking lifestyle measures to treat diabetes by strictly controlling blood glucose will, in turn, reduce diabetic nephropathy rate of progression.

 

• Angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARB’s) may prevent or in some cases, reverse rate of kidney disease progression (6), and reduce proteinuria.

 

• Hypertension:
  • Hypertension is the most common cause of kidney disease after diabetes mellitus.
  • Hypertension should be diagnosed early and treated before it causes kidney disease or progression of chronic kidney disease.

 

• Medication affect upon the kidneys:
  • Avoid contrast and nephrotoxic drugs whenever possible.
  • Avoid contrast with CT scans and MRI scans when it is not necessary.
  • Patients should be hydrated well prior to a procedure which uses contrast.
  • Before a procedure with contrast, MRI or CT scan, increase hydration over the 24 hours prior.
  • Avoid contrast in diabetics taking metformin within 48 hours which may lead to a complication of lactic acidosis.
  • Patients should avoid frequent or long term use of non-steroidal anti-inflammatory drugs.
  • ACE inhibitors should be held in setting of acute kidney injury, or abrupt increase in creatinine shortly after starting ACE inhibitors which may be a sign of renal artery stenosis.

 

• Prostate disease such as benign prostatic hyperplasia, prostate cancer or kidney stones may lead to renal failure if obstruction is not promptly relieved. For these conditions, referral to Urology is often necessary to relieve the obstruction.

 

• Aneurysms, malformations, renal artery stenosis, and peripheral vascular disease in the arteries supplying the kidneys may result in renal failure. The majority of these diseases are caused by atherosclerosis. Western style diet, sedentary lifestyle, smoking, diabetes, uncontrolled high blood pressure, and hyperlipidemia results in atherosclerosis. Good lifestyle choices will prevent atherosclerosis to a significant degree.

 

• Conditions related to low blood volume or low perfusion states such as heart failure, liver disease, dehydration, blood loss, and diarrhea may result in renal failure.
  • Treatment of the underlying cause is indicated.
  • Dehydration should be avoided at all times by drinking adequate water unless fluid restriction is necessary for heart failure or other conditions.
  • For severe dehydration such as in heat illness, or infectious diarrhea, a rehydration regimen with 4-8 ounces of water alternating with the same amount of Gatorade or Pedialyte may be consumed every 5-10 minutes with use of a timer if necessary over the course of 2 hours. If oral fluid intake is not possible in setting of severe dehydration, intravenous fluids are required.

 

• Chronic kidney disease Integrative Medicine options:
  • Chronic kidney disease and Pycnogenol:
    • Ramipril (5mg twice daily) plus Pycnogenol (50 mg 3 times/day) significantly further lowered blood pressure (BP) when compared to the group taking Ramipril alone to 122.2/85.3 mmHg vs. 128.2/90.2 mmHg after 6 months (8). Ramipril alone reduced urinary protein by 22% vs. 52.7% with the addition of Pycnogenol. Lowered fasting blood glucose, and significant weight loss (BMI 26.5 decreased to 25.0) was also noted only in the group with addition of Pycnogenol after 6 months (8).
    • Urine albumin levels decreased significantly in the ramipril plus Pycnogenol group (-52 mg/day) vs. ramipril alone (-23 mg/day only), and improved blood flow to the kidneys (9).
  • Chronic kidney disease and coenzyme Q10: Coenzyme Q10 (CoQ10) at 60 mg, 3 times daily appeared to reduce the requirement for a group of patients to be on hemodialysis (10). 36.2% of the CoQ10 group vs. 90.0% of the placebo group required hemodialysis, and there was also a significant improvement in creatinine clearance, serum urea, and urine output in the CoQ10 group (10).

 

• Kidney disease and comparison of phosphate binders: Navaneethan SD et al found (11):
  • Treatment with calcium salts resulted in a significantly lower phosphorus and parathyroid hormone levels compared with sevelamer.
  • Sevelamer had a lower risk of hypercalcemia by 53%, but was 39% more likely to cause gastro-intestinal side-effects compared to calcium salts.

 

• Reducing or eliminating red meat may reduce the risk of worsening kidney disease (12)

 

 

References:

1.Levi TM1, Souza SP2, Magalhães JG2, Carvalho MS2, Cunha AL2, Dantas JG3, Cruz MG4, Guimarães YL4, Cruz CM5.Comparison of the RIFLE, AKIN and KDIGO criteria to predict mortality in critically ill patients. [Article in English, Portuguese]. Rev Bras Ter Intensiva. 2013 Oct-Dec;25(4):290-296. http://www.ncbi.nlm.nih.gov/pubmed/24553510

 

2.Roy AK1, Mc Gorrian C, Treacy C, Kavanaugh E, Brennan A, Mahon NG, Murray PT. A Comparison of Traditional and Novel Definitions (RIFLE, AKIN, and KDIGO) of Acute Kidney Injury for the Prediction of Outcomes in Acute Decompensated Heart Failure. Cardiorenal Med. 2013 Apr;3(1):26-37. http://www.ncbi.nlm.nih.gov/pubmed/23801998

 

3.Levey AS1, de Jong PE, Coresh J, El Nahas M, Astor BC, Matsushita K, Gansevoort RT, Kasiske BL, Eckardt KU. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney Int. 2011 Jul;80(1):17-28. http://www.ncbi.nlm.nih.gov/pubmed/21150873

 

4.American Diabetes Association. Standards of medical care in diabetes–2010. Diabetes Care. 2010 Jan;33 Suppl 1:S11-61. http://www.ncbi.nlm.nih.gov/pubmed/20042772

 

5.Anabtawi A1, Mathew LM. Improving compliance with screening of diabetic patients for microalbuminuria in primary care practice. ISRN Endocrinol. 2013 Oct 9;2013:893913. http://www.ncbi.nlm.nih.gov/pubmed/24224095

 

6.Ruggenenti P1, Cravedi P, Remuzzi G. Mechanisms and treatment of CKD. J Am Soc Nephrol. 2012 Dec;23(12):1917-28. http://www.ncbi.nlm.nih.gov/pubmed/23100218

 

7.Nawaz FA1, Larsen CP, Troxell ML. Membranous nephropathy and nonsteroidal anti-inflammatory agents. Am J Kidney Dis. 2013 Nov;62(5):1012-7. http://www.ncbi.nlm.nih.gov/pubmed/23773370

 

8.Stuard S, Belcaro G, Cesarone MR, et al. Kidney function in metabolic syndrome may be improved with Pycnogenol®. Panminerva Med. 2010 Jun;52(2 Suppl 1):27-32. http://www.ncbi.nlm.nih.gov/pubmed/20657531

 

9.Cesarone MR, Belcaro G, et al. Kidney Flow and Function in Hypertension: Protective Effects of Pycnogenol in Hypertensive Participants—A Controlled Study. J Cardiovasc Pharmacol Ther. 2010 Mar;15(1):41-6. http://www.ncbi.nlm.nih.gov/pubmed/20097689

 

10.Singh RB, Khanna HK, Niaz MA. Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in chronic renal failure: discovery of a new role. J Nutr Environ Med. 2000;10(4):281-288. http://informahealthcare.com/doi/abs/10.1080/13590840020013266?journalCode=cjne

 

11.Navaneethan SD, Palmer SC, Craig JC, Elder GJ, Strippoli GF. Benefits and harms of phosphate binders in CKD: a systematic review of randomized controlled trials. Am J Kidney Dis. 2009 Oct;54(4):619-37. http://www.ncbi.nlm.nih.gov/pubmed/19692157

 

12.Lew QJ, Jafar TH, Koh HW, Jin A, Chow KY, Yuan JM, Koh WP. Red Meat Intake and Risk of ESRD. J Am Soc Nephrol. 2016 Jul 14. http://www.ncbi.nlm.nih.gov/pubmed/27416946

kidney image courtesy of dream designs