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Donna Myers, M.D.
11-05-2010
- Renal disease in diabetes may be caused by diabetes, or may be of other etiology, co-existing with diabetes.
- In diabetes, persistant proteinuria without other cause, is the first sign of diabetic nephropathy.
- Diabetes is the most common cause of end-stage renal disease (ESRD) in the world (Harvey).
- Although only 25% of type 1 and 2 diabetes patients will develop classic diabetic nephropathy, hypertensive nephropathy, nephrosclerosis, atherosclerotic renal artery stenosis, non-diabetic glomerulopathies, acute and chronic pyelonephritis, papillary necrosis and type IV renal tubular acidosis (RTA) are all more prevalent in diabetes (Mazzucco).
- The majority of proteinuric renal disease in both types 1 and 2 diabetes with a gradual onset after 10 years of diabetes is due to diabetic nephropathy (Mazzucco, Harvey).
- Staging kidney disease requires only a spot urine albumin to creatinine ratio, a serum creatinine level, and a calculated GFR using the modified MDRD formula (see National Kidney Foundation GFR Calculator).
- Chronic kidney disease (CKD) is classified by urinary albumin and glomerular filtration rate (GFR) in ml/min/1.73 m2. Stage 1 = proteinuria, GFR > 90; Stage 2 = proteinuria, GFR 60 - 89; Stage 3 = GFR 30-59; Stage 4 = GFR 15-29; Stage 5 = GFR < 15.
- Further evaluation includes a complete urinalysis, serum electrolytes, and renal ultrasound; renal biopsy may be necessary in some cases.
- Type IV RTA (hyporeninemic hypoaldosteronism) should be suspected in any patient with diabetes and hyperkalemia in the absence of advanced kidney disease, K+ supplements or K+ sparing diuretics; a mild metabolic acidosis is usually present with a normal anion gap.
- Suspect renal artery stenosis if accelerated hypertension, severe peripheral vascular disease, abdominal and femoral bruits, asymmetric kidneys (1.5 cm discrepancy), and/or a rise in serum creatinine > 0.6 mg/dL with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARBs).
- Laboratory signs of renal disease include proteinuria, decreased glomerular filtration rate, elevated blood urea nitrogen, hyperkalemia and type 4 renal tubular acidosis.
- Physical findings of patients with early renal disease include hypertension and edema. Late findings include uremic fetor, asterixis, peripheral neuropathy, altered mental status and seizures.
- Early symptoms of renal disease include anorexia, a "metal" taste in the mouth, early morning nausea, frothy urine (with > 3 g proteinuria), nocturia, fatigue and excessive sleeping. Late symptoms include difficulty concentrating, loss of lean body mass, restless legs and lethargy.
- There are no agreed upon guidelines for glycemic control in diabetic patients with CKD, but good diabetic control may slow progress.
- With CKD stages 1 - 4, follow general guidelines and maintain HbA1c between 6-7%.
- Interference with HbA1c assay by uremia, acidosis and shortened red blood cell survival may spuriously affect HbA1c levels in stage 5 CKD and ESRD.
- Follow blood pressure (BP) guidelines of JNC7 (< 130/80 mmHg) with attention to postural changes from medications and diabetic autonomic neuropathy.
- Reduce proteinuria by renin angiotensin system (RAAS) blockade in all renal patients.
- Limit dietary sodium to 2.0 grams/day (100 mM), including "hidden" dietary sodium.
- Uncontrollable hyperkalemia and a rise in serum creatinine > 0.6 mg/dL limit therapy.
- Obesity should be addressed with dieting and exercise to reduce hypertension, obstructive sleep apnea and secondary focal and segmental glomerulosclerosis caused by hyperfiltration across glomerular capillary membranes.
- Hyperlipidemia management may reduce the burden of atherosclerotic disease which often accompanies diabetic renal disease.
- Cigarette smoking cessation reduces proteinuria.
- Patients with diabetes and progressive renal disease may develop poor glucose control due to reduced tissue sensitivity to insulin and require increasingly higher doses of insulin therapy.
- As patients approach ESRD, insulin requirements may decline due to reduced insulin clearance from the kidneys.
- Avoid metformin in stages 3, 4 and 5 CKD (increased risk of lactic acidosis). Contraindicated with creatinine >1.5 mg/dl.
- Dose-adjust all diabetes medications for reduced GFR (see Table below).
- Type IV RTA should be treated with dietary K+ limitation and avoidance of K+ supplements; discontinuation of ACE-I or ARB therapy may become necessary in some patients.
- Lifestyle: exercise, limited alcohol, weight loss; limit sodium to 2 grams/day (100mM).
- Check BP supine and standing
- If diuretics needed, use thiazides diuretics in stages 1-3 CKD; loop diuretics (furosemide), in stages 4-5 CKD, may require twice daily dosing; potassium-sparing diuretics used cautiously if at all in stages 3, 4 and 5 CKD.
- RAAS blockade with ACE-I and ARBs indicated for urinary protein reduction, reno-protection and HTN control; also improves cardiac outcome if CHF or LV dysfunction.
- Combining ACE and ARB therapy may further reduce proteinuria but also worsen overall renal outcome; monitor closely.
- Initiation or increases in ACE-I or ARBs should be monitored within 7 days for hyperkalemia and acute kidney injury.
- The combination of diuretics and ACE-I or ARB therapy in a patient who becomes volume depleted may precipitate acute renal failure.
- Non-selective beta-blockers improve insulin sensitivity and reduce proteinuria in contrast to beta-1 selective blockers.
- Non-dihydropyridine agents are more effective in reducing proteinuria but may cause myocardial depression.
- Avoid NSAIDS in all patients with CKD; with diabetes, further increase risk of papillary necrosis.
- Radiographic i.v. contrast is nephrotoxic in a dose-dependent manner; risk factors include diabetes, proteinuria, ineffective renal perfusion (CHF, Cirrhosis) and CKD stages 3-5.
- If contrast is essential, use low osmolar nonionic contrast and prophylactic measures one day before and the day of the dye-load.
- Prophylactic measures: N-acetylcysteine 600 mg PO twice-daily x 2 days, saline hydration, and discontinuation of ACE-I/ARBs and diuretics.
- Minimizing the dye load is most important.
- Gadolinium, to enhance MRI studies, used only with caution, in early CKD, and contraindicated with stages 4-5 CKD due to risk of nephrogenic systemic fibrosis.
- Bisphosphonates contraindicated in patients with a GFR < 30 ml/min (stages 4-5 CKD).
- Phosphate-containing bowel preps may cause severe hyperphosphatemia and acute, irreversible kidney injury; avoid with CKD.
- Annual screening for CKD starting with diagnosis of T2DM and after 5 years of T1DM using pot urinary albumin:creatinine ratio, serum creatinine, estimated GFR.
- Refer patients with diabetes and stage 1-2 chronic kidney disease in whom the renal diagnosis is unclear.
- When feasible, refer to nephrology at stage 3 CKD.
- Stages 4-5 pre-ESRD patients should be followed closely by nephrology.
- Inform the patient of the therapeutic goals of management.
- Therapy with RAAS blockade and diuretics is a double-edged sword: risk is that these agents can cause acute kidney injury from dehydration.
- In the absence of co-existing diabetic retinopathy, diabetic nephropathy is uncommon and other etiologies for renal disease should be considered.
- Many diabetes medications including insulin will need dose adjustment as renal disease progresses.
- Bakris GL, Sowers JR, American Society of Hypertension Writing Group;
ASH position paper: treatment of hypertension in patients with diabetes-an update.;
J Clin Hypertens (Greenwich);
2008; Vol.
10; pp.
707-13; discussion 714-5;
ISSN:
1524-6175;
PUBMED: 18844766
Rating:
Basis for recommendation
Comments:A consensus report from the American Society of Hypertension (ASH) on managing HTN in patients with diabetes.
- [no author listed];
K/DOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease;
Am J Kidney Dis;
2007; Vol.
49(2 Suppl 2): S12; pp.
PUBMED: 17276798
Rating:
Basis for recommendation
Comments:The Kidney Disease Outcomes Quality Initiative (K/DOQI) has published this comprehensive reference text for the clinician involved in managing diabetic patients with chronic kidney disease; reviews national (USA) guidelines for management and the rationale for these therapies
- Chobanian AV, Bakris GL, Black HR, et al.;
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.;
JAMA;
2003; Vol.
289; pp.
2560-72;
ISSN:
0098-7484;
PUBMED: 12748199
Rating:
Basis for recommendation
Comments:A landmark report updating stricter guidelines for blood pressure control.
- Bakris GL, Williams M, Dworkin L, et al.;
Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group.;
Am J Kidney Dis;
2000; Vol.
36; pp.
646-61;
ISSN:
1523-6838;
PUBMED: 10977801
Rating:
Basis for recommendation
Comments:National guidelines on hypertension management in patients with diabetes and CKD.
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