Diabetic Renal Disease

In 1996, two studies showed that calcium-channel blockers may have an important role in preventing renal failure in diabetic patients. Another study found that progression of renal disease in type 1 diabetes mellitus parallels that in type 2 diabetes mellitus.

Calcium-Channel Blocker Improved Glomerular Filtration Rate

Mosconi L, Ruggenenti P, Perna A, Mecca G, Remuzzi G. Nitrendipine and enalapril improve albuminuria and glomerular filtration rate in non-insulin dependent diabetes. Kidney Int. 1996; 49:S91-3.

Evidence clearly shows that angiotensin-converting enzyme (ACE) inhibitors delay the onset of nephropathy in patients with type 1 diabetes. Data increasingly indicate that ACE inhibitors are similarly efficacious in patients with type 2 disease [1, 2]. Some authors have suggested that calcium-channel blockers may also have a role in preventing renal disease in diabetic patients [3]. Mosconi and colleagues evaluated the relative ability of both classes of drugs to prevent nephropathy, particularly in patients with type 2 diabetes.

Sixteen patients with type 2 diabetes, microalbuminuria (urinary albumin excretion rate, 20 to 200 mg/d), hypertension, and biopsy-proven diabetic nephropathy were recruited. All patients stopped receiving antihypertensive therapy for 2 weeks and received placebo for 1 month. The 13 patients who complied with this protocol were entered into a trial in which they were given nitrendipine, a calcium-channel blocker (dosage titrated to a maximum of 20 mg twice daily), or enalapril, an ACE inhibitor (maximum dosage, 10 mg twice daily). (Nitrendipine is a short-acting dihydropyridine that has not yet been approved for use in the United States but is available in Europe.) Outcome measures were diastolic blood pressure, urinary albumin excretion rate, glomerular filtration rate (inulin clearance), and renal plasma flow. These variables were measured at 15 and 27 months.

At 15 months, the glomerular filtration rate had improved in both groups-by 33% in enalapril recipients and 39% in nitrendipine recipients. By 27 months, the urinary albumin excretion rate had decreased steadily in both groups.

Although small, this study was carefully done and provides evidence that calcium-channel blockers can improve glomerular filtration in patients with type 2 diabetes and nephropathy. Moreover, the calcium-channel blocker was more effective than the ACE inhibitor in decreasing diastolic blood pressure.

It has been thought that ACE inhibitors delay nephropathy by decreasing pressure in the efferent glomerular arteriole. However, in vitro studies suggest that ACE inhibitors may directly alter function of the mesangial cell, the key cell responsible for producing the extra matrix that tends to damage the glomerulus. Because calcium-channel blockers work by different mechanisms, they had been thought not to be as effective as ACE inhibitors. These authors, however, postulate that the drugs' superior effect on decreasing blood pressure may simply cause direct decreases in intraglomerular pressure.

Despite its limitations, this study is important for three reasons. First, it suggests that two classes of drugs may be able to reverse diabetic nephropathy, as indicated by the increase in glomerular filtration rate. Second, it showed the beneficial effects of nitrendipine, a calcium-channel blocker. Finally, the authors were careful to establish that the participants had diabetic nephropathy: In up to 25% of patients with type 2 diabetes and nephropathy, nephropathy will be caused by something other than diabetes.

Effects of Antihypertensive Agents on the Kidney Were Compared

Bakris GL, Coplet JB, Vicknair N, Sadler R, Leurgans S. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int. 1996; 50:1641-50.

Despite Mosconi and colleagues' study, we still lack good evidence on the effects of specific calcium-channel blockers on renal hemodynamic function. A large clinical trial is needed. In the meantime, Bakris and colleagues designed a small study to determine whether the nondihydropyridine calcium-channel blockers were as effective as the dihydropyridines. Table 1 lists the classes of calcium-channel blockers.

Fifty-two patients (mean age, 63 years) with type 2 diabetes and nephropathy (not biopsy proven) were randomly assigned to receive one of three agents: lisinopril (an ACE inhibitor), atenolol (a ß-blocker), or either verapamil or diltiazem (nondihydropyridine calcium-channel blockers). Mean baseline creatinine clearance was about 60 mL/min per 1.73 m². All drug doses were titrated to optimize blood pressure. Outcomes were blood pressure control, creatinine clearance, and albumin excretion; these variables were measured every 6 months for 6 years.

Creatinine clearance decreased at a similar rate among those taking lisinopril (1.0 mL/min per year per 1.73 m²) and either calcium-channel blocker (1.4 mL/min per year per 1.73 m²). This was much slower than the decrease seen among those taking atenolol (3.5 mL/min per year per 1.73 m²). Lisinopril and the calcium-channel blockers reduced proteinuria to an equal degree, but atenolol was significantly less effective than the other agents.

The authors concluded that patients with renal insufficiency secondary to type 2 diabetes achieved a similar slowing of decline with the nondihydropyridine calcium-channel blockers and lisinopril but much less improvement with atenolol; this finding was seen even though all drugs effectively controlled diastolic blood pressure. The slowing of the progression of renal disease correlated with decreases in proteinuria.

This study did have several limitations. First, it was an open-label study. Second, the atenolol group did not achieve equal lowering of systolic blood pressure. Third, the authors used creatinine clearance as an outcome. This variable is of limited usefulness in these kinds of studies because it tends to underestimate the true decrement in glomerular filtration rate in advanced renal disease. Creatinine secretion is enhanced as the serum creatinine level increases, thereby elevating the rate of creatinine excretion above that achieved by filtration alone.

Taken together, the studies by Mosconi and Bakris and their colleagues lend some support to the concept that calcium-channel blockers might be useful in some patients with diabetic nephropathy. We believe that ACE inhibitors are clearly still the agents to be used for first-line therapy. However, for patients who cannot tolerate ACE inhibitors, clinicians can feel a bit more comfortable about using calcium-channel blockers. More comprehensive and longer-term studies must be done to determine which specific agent in this class is superior.

Nephropathy in Type 2 Diabetes Was Predictable

Nelson RG, Bennett PH, Beck GJ, Tan M, Knowler WC, Mitch WE, et al. Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic Renal Disease Study Group. N Engl J Med. 1996; 335:1636-42.

We understand a great deal about the natural history of renal disease among patients with type 1 diabetes [4, 5], but one question always arises: How much of our knowledge can we extrapolate to patients with type 2 diabetes?

Nelson and colleagues measured glomerular function every 6 to 12 months for 4 years in 194 Pima Indians selected to represent different stages in the development and progression of diabetic renal disease. Glomerular filtration rate, renal plasma flow, urinary albumin excretion, and blood pressure were measured at each examination. Because Pima Indians are a carefully followed cohort, the onset of diabetes can be pinpointed more accurately.

The mean glomerular filtration rate ±SD was 143 ± 7 mL/min in patients with newly diagnosed diabetes, 155 ± 7 mL/min in those with microalbuminuria, and 124 ± 7 mL/min in those with macroalbuminuria. The glomerular filtration rate in patients with normal glucose tolerance was 123 ± 4 mL/min. During the 4 years of follow-up, the glomerular filtration rate increased by 18% in patients who had newly diagnosed diabetes at baseline (P = 0.008) and decreased by 3% in patients with microalbuminuria at baseline (P > 0.2) and by 35% in patients with macroalbuminuria at baseline (P < 0.001). Higher baseline blood pressure predicted increased urinary albumin excretion (P = 0.006), and higher baseline urinary albumin excretion predicted a decline in glomerular filtration rate (P < 0.001). The initial glomerular filtration rate did not predict worsening albuminuria.

This study suggests that type 1 and type 2 diabetes affect the kidney similarly. The glomerular filtration rate is elevated at the onset of diabetes and then declines progressively after macroalbuminuria develops. It is important to note that the researchers initiated treatment with ACE inhibitors once they had established that the drugs were effective in blunting nephropathy among patients with type 1 diabetes. These findings support a unitarian approach to the prevention and treatment of nephropathy in all forms of diabetes.

Chronic Renal Insufficiency

In 1996, ACE inhibitors were found to have positive effects in patients who had renal disease other than renal decline due to diabetes. In addition, a meta-analysis provided evidence that dietary protein restriction may delay the onset of end-stage renal disease.

Enalapril Slowed Decline in Persons without Diabetes

Ihle BU, Whitworth JA, Shahinafar S, Cnaan A, Kincaid-Smith PS, Becker GJ. Angiotensin-converting enzyme inhibition in nondiabetic progressive renal insufficiency: a controlled double-blind trial. Am J Kidney Dis. 1996; 27:489-95.

A grand unified theory of renal disease states that once a certain number of nephrons have been lost, both systemic and intraglomerular hypertension work to accelerate the process of kidney disease, no matter what the cause. Angiotensin-converting enzyme inhibitors have received much attention for preventing the progression of renal disease in diabetic patients, but we also are now seeing evidence that they prevent the progression of other renal disease, perhaps by blunting the hypertensive process.

In a 2-year clinical trial, Ihle and colleagues recruited 70 hypertensive patients with severe renal disease of various causes (glomerulonephritis was the most common). Patients were randomly assigned to receive either placebo or enalapril (5 mg/d). Plasma creatinine levels ranged from 2.8 to 6.8 mg/dL, and the mean creatinine clearance was 15 mL/min per 1.73 m². Outcomes were the rate of change in glomerular filtration rate and urinary protein excretion.

Enalapril reduced the rate of deterioration of renal disease, as measured by both glomerular filtration rate (P = 0.038) and creatinine clearance (P = 0.031). This renal protective effect was shown to occur in addition to the antihypertensive effect of enalapril. Proteinuria decreased in enalapril recipients (P = 0.007) and increased slightly in placebo recipients (P = 0.051). However, hyperkalemia occurred in about a third of the patients in the enalapril group; these patients required sodium polystyrene sulfonate.

Several conclusions can be drawn from this study; as with any single study, however, these conclusions must be considered somewhat tentative. First, enalapril decreases the rate of progression of renal disease in patients without diabetes as well as those with diabetes. Second, this effect occurs in addition to the renal protection afforded by the decreased blood pressure. Third, severe proteinuria was an independent risk factor for renal decline; this finding suggests that aggressive treatment to decrease protein excretion may be a further benefit to patients. However, it seems clear that patients with renal insufficiency who are treated with ACE inhibitors must be carefully monitored to ensure that dangerous hyperkalemia does not develop.

Protein Restriction Slowed Renal Decline

Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med. 1996; 124:627-32.

Postponing or even preventing dialysis or transplantation should be the major prevention goal in patients with renal insufficiency. Dietary protein restriction has been supported by many experts, but clinical trials have not consistently shown that it slows the progression of chronic renal disease. In fact, a large recent trial showed no significant benefit of dietary modification [6]. One of the authors of that study decided to pool data from it and other studies into a meta-analysis that assessed the efficacy of protein restriction.

The authors reviewed the English-language medical literature published from 1966 through 1994 to find studies that examined the effect of low-protein diets in humans with chronic renal disease. A total of 1413 patients in five studies of nondiabetic renal disease and 108 patients in five studies of type 1 diabetes were included. The authors selected randomized, controlled studies for nondiabetic renal disease and randomized, controlled studies or time-controlled studies with a nonrandomized crossover design for diabetic nephropathy.

In the studies of nondiabetic renal disease, a low-protein diet significantly reduced the risk for renal failure or death (relative risk reduction, 33% [95% CI, 11% to 50%]). In the studies of disease caused by type 1 diabetes, a low-protein diet slowed the increase in urinary albumin excretion or the decline in glomerular filtration rate or creatinine clearance (relative risk reduction, 44% [CI, 23% to 60%]). No meaningful differences in mean arterial blood pressure were found between diet groups.

Compliance is the most difficult issue in prescribing a diet that contains as little as 0.4 g of protein per kilogram of body weight per day. In fact, in these studies, as in real life, compliance probably was not great. Nonetheless, the pooled data did show substantial benefit for patients with renal insufficiency, perhaps so much benefit that dialysis or transplantation was at least delayed. However, those clinical outcomes were not measured. For clinical practice, we believe that the evidence is now adequate to support both the prescription of protein restriction and the use of ACE inhibitors.

Despite these positive benefits, each treatment should be used with considerable care. Because malnutrition is a common problem in patients starting dialysis, protein restriction needs to be tempered by the patient's overall nutritional needs. In fact, truly adequate dietary treatment requires the consultation of a dietitian. When prescribing ACE inhibitor therapy, clinicians should note that because renal artery stenosis is probably not rare, early follow-up of the serum creatinine level is worthwhile after treatment begins.

Drugs and the Kidney

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known renal toxins, but one study has found that the absolute risk for acute renal failure among NSAID users in the community was low. Another class of kidney toxins, the aminoglycoside antibiotics, was found to probably be safer when given once a day.

Nonsteroidal Anti-Inflammatory Drugs Increased the Incidence of a Rare Event

Perez Gutthann S, Garcia Rodriguez LA, Raiford DS, Duque Oliart A, Ris Romeu J. Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure. Arch Intern Med. 1996; 156:2433-9.

Nonsteroidal anti-inflammatory drugs are among the most widely used drugs in the United States, both by prescription and over the counter. The precise community prevalence of NSAID-induced acute renal failure remains unknown. These drugs can induce acute renal failure through hemodynamic effects from prostaglandin inhibition or by causing interstitial nephritis. Perez Gutthann and colleagues sought to determine whether NSAIDs used in the community resulted in a measurable increase in hospitalization for acute renal failure.

In a case–control study, 228 392 persons who received at least one NSAID prescription between 1982 and 1986 were identified and followed until adverse outcomes occurred or the study ended. The authors identified 329 patients who were admitted to the hospital with kidney-related diagnoses. Of the 329, 23 were excluded because of an antecedent neoplasm. Medical records of the 306 remaining patients were carefully reviewed; 28 met the diagnostic criteria for acute renal failure.

The incidence of hospitalization for acute renal failure was 2 per 100 000 person-years for patients without exposure to NSAIDs. The odds ratio for hospitalization for acute renal failure among current NSAID users was 4.1 (CI, 1.5 to 10.8). Other major risk factors are shown in Table 2. The use of aspirin and other nephrotoxic drugs was also associated with more hospitalizations.

Thus, hospitalization for acute renal failure was unusual, but the use of NSAIDs increased the risk. The absolute risk, however (even among NSAID users), was low. For example, the risk for acute renal failure for a person initiating NSAID therapy was only about 1 in 67 000 person-years. Given the enormous number of persons who are using these drugs, however, even such a low incidence of toxicity may result in a substantial absolute number of patients with renal damage. Two other points might also be extrapolated from these data. First, the increased risk for acute renal failure during the first month of NSAID therapy may reflect previously unrecognized renal insufficiency in some patients. Second, for patients at higher-than-average risk for nephrotoxicity, a follow-up serum creatinine test is an inexpensive way to avoid harming patients who have begun taking NSAIDs.

Single Dose of Aminoglycoside Was Effective and Safe

Barza M, loannidis JP, Cappelleri JC, Lau J. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ. 1996; 312:338-45.

Aminoglycosides remain a critical class of antibacterial drugs, and their importance may increase as microbial resistance to other antibiotics increases. Single-dose aminoglycoside regimens have been designed to capitalize on aminoglycoside concentration-dependent killing and, in theory, to simultaneously reduce the risk for renal toxicity caused by excessive drug accumulation. Does the hypothesis prove true in practice?

In a meta-analysis of clinical trials, Barza and colleagues compared the relative efficacy and toxicity of single daily doses of aminoglycosides with the efficacy and toxicity of multiple daily doses. The authors found 21 clinical trials published from 1966 to 1995. From these, they identified 3091 patients with bacterial disease, most of whom had no known kidney disease at enrollment. Outcomes were treatment failure, ototoxicity, nephrotoxicity, and death.

The relative risk for clinical failure with single dosing was lower than that seen with multiple dosing, although the improvement did not reach the conventional level of statistical significance (relative risk for failure, 0.83 [CI, 0.57 to 1.21]). Single-dose regimens seemed to be more efficacious against Pseudomonas isolates. At the same time, the single-dose regimen also caused less nephrotoxicity (relative risk, 0.74 [CI, 0.54 to 1.00]). No differences were seen in the incidence of ototoxicity or overall mortality rates.

Another meta-analysis, which asked similar questions and was somewhat more rigorous, showed no clinically or statistically significant differences in any outcome [7]. However, the conclusions of these two analyses are clinically important. First, single-dose aminoglycoside therapy in patients without preexisting renal disease is as effective as multiple-dose therapy. Second, single-dose therapy may reduce the risk for nephrotoxicity, although these meta-analyses disagree slightly about that point. Third, single-dose therapy does not increase the risk for death or other toxic effects of these agents. Finally, single daily dosing is more convenient and less expensive.

End-Stage Renal Disease

For the most part, general internists are responsible for managing patients with chronic renal failure who have not begun dialysis. As renal function continues to decline, it is important to consider the patient's future needs.

Fewer Fistulas Are Being Placed

Hirth RA, Turenne MN, Woods JD, Young EW, Port FK, Pauly MV, et al. Predictors of type of vascular access in hemodialysis patients. JAMA. 1993; 276:1303-8.

About 270 000 patients in the United States are currently undergoing dialysis, and about 60 000 begin long-term dialysis each year. The average patient spends about 2 weeks per year in the hospital, and the most common single reason for admission for management is complications of vascular access. Two types of access are available-a native fistula, in which an artery is directly connected to a vein, or a synthetic graft, which consists of polytetrafluoroethylene synthetic tubing. Studies have indicated that fistulas result in greater patency and fewer infections and other complications compared with synthetic grafts [8, 9].

Hirth and colleagues set out to identify what determines the type of vascular access placed in patients undergoing hemodialysis and to track trends in placement. The U.S. Renal Data System Special Studies database was used to identify 2741 patients who began undergoing dialysis in 1986-1987 and 1409 patients who began in 1990. The researchers used multivariate analyses to determine factors associated with the two types of access. They found that the use of synthetic grafts increased from 51% in 1986-1987 to 65% in 1990. Other significant factors and geographic trends are shown in Table 3.

Surgeons who are proficient in the creation of native arteriovenous fistulas are increasingly uncommon in the United States. In fact, 10% of U.S. vascular surgeons create 70% of the fistulas. The creation of the longer-lasting fistulas seems to be a dying art. The message for the internist is also important. Access sites in the arm need to be protected. The number of these access sites is finite-the upper and lower parts of each arm are the main sites available. If venipuncture is repeatedly done in these sites, hematomas can form or the anatomy can be distorted; if either of these events occur, the access site will no longer be usable. Because access takes 6 to 8 weeks to mature, consideration of early placement may prevent patients from undergoing dialysis through temporary central venous catheters, which are fraught with infection problems and make hemodialysis less efficient.

Anemia Was Associated with Cardiomyopathy

Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. The impact of anemia on cardiomyopathy, morbidity, and mortality in end-stage renal disease. Am J Kidney Dis. 1996; 28:53-61.

Heart disease is the leading cause of death in patients with end-stage renal disease, and it is believed that anemia contributes to heart disease by causing left ventricular hypertrophy during the period before the end stage. In patients undergoing dialysis, left ventricular hypertrophy is an independent risk factor for early death. Foley and colleagues explored the hypothesis that interrupting the process by preventing the anemia results in a lower prevalence of left ventricular hypertrophy. The authors' specific purpose was to determine the association between anemia and echocardiographic cardiac disease in patients undergoing dialysis.

A cohort of 432 Canadian patients with end-stage renal disease (261 undergoing hemodialysis and 171 undergoing peritoneal dialysis) was followed prospectively for an average of 41 months. Clinical and echocardiographic data were obtained at the beginning of the study and were measured throughout the study. Adjustments were made for age, diabetes, ischemic heart disease, blood pressure, and serum albumin level.

A decrease in hemoglobin concentration of 1 g/dL was associated with a 49% increased likelihood of left ventricular dilatation, a 55% increased likelihood of poor ejection fraction, and a 14% increased likelihood of death. This relatively short study showed no specific association between anemia and coronary artery disease.

Anemia was associated with left ventricular dysfunction, so the message suggested by this study is simple: Anemia should be treated early, and it should be treated before dialysis begins. The use of erythropoietin, especially in patients who have renal failure accompanied by severe anemia, is certainly worth considering in light of these provocative findings. At the same time, however, it is important to point out that this study did not directly explore the effect of reversing the anemia.

Important Miscellany

Finally, two studies addressed common scenarios. For women with moderate to severe renal disease, pregnancy was relatively dangerous. In patients with hypertensive emergencies, one review suggested that sublingual use of nifedipine should be abandoned.

Pregnancy with Severe Renal Disease Was Dangerous

Jones DC, Hayslett JP. Outcome of pregnancy in women with moderate or severe renal insufficiency. N Engl J Med. 1996; 335:277-8.

Internists have become more involved in the care of women. They now commonly see women who wish to become pregnant, including those with renal disease. The impact of renal disease on pregnancy has not been studied in detail. The general view has been that pregnancy is a bad idea among women with any renal disease.

In a multicenter study, Jones and Hayslett determined the maternal and obstetric complications and outcomes of pregnancy in 67 women (82 pregnancies) with primary renal disease. Renal insufficiency was defined as a serum creatinine concentration of at least 1.4 mg/dL. Gestations had to continue beyond the first trimester to be included in the analysis.

Mean serum creatinine concentration increased from 1.9 ± 0.8 mg/dL in early pregnancy to 2.5 ± 1.3 mg/dL in the third trimester. The frequency of hypertension increased from 28% to 48%, and the frequency of high-grade proteinuria (urinary protein excretion > 3.0 g/dL) increased from 23% to 41%. Of the 70 pregnancies for which data were available during pregnancy and immediately postpartum, pregnancy-related loss of maternal renal function occurred in 43%. Obstetric complications included a high rate of preterm delivery (59%) and growth retardation (37%). However, the infant survival rate was 93%.

The pattern of decline in renal function depended on the initial level of function. Renal function stayed stable in most patients who had serum creatinine concentrations less than 2.0 g/dL. However, patients with worse renal function in the first trimester had relatively poor outcomes: Seven of 20 patients progressed to end-stage renal disease.

Therefore, among pregnant women with moderate or severe renal insufficiency, the rate of complications from worsening renal function, hypertension, and obstetric difficulties are increased but fetal survival remains high. In the counseling of women with moderate to severe disease who are considering pregnancy, it is important to realize that they have a high likelihood of progression of renal disease.

Sublingual Use of Nifedipine May Be Risky

Grossman E, Messerli FH, Grodzicki T, Kowey P. Should a moratorium be placed on sublingual nifedipine capsules given for hypertensive emergencies and pseudoemergencies? JAMA. 1996; 276:1328-31.

Nifedipine, a calcium-channel blocker, causes peripheral vasodilatation and has mild negative inotropic and chronotropic effects. It induces hypotension 5 to 10 minutes after administration. Because of these properties, nifedipine given sublingually has become a popular therapy for hypertensive emergencies. However, such therapy is associated with several problems. Most important, outcomes data have not been available to assess the efficacy or safety of sublingual use of the drug. Second, sublingual absorption of nifedipine has been shown to be negligible. Third, the manner in which the drug is administered varies greatly among hospitals, with consequent variation in the absorption of the drug.

Grossman and colleagues analyzed the available published data on toxicity. They found reports of 16 major complications, including hemiparesis, loss of consciousness, acute myocardial infarction, syncope, and death. Adverse effects occurred with all commonly used doses.

However, the authors could not identify a denominator (that is, the total number of patients given the drug), nor did they measure the incidence of major complications in patients with this serious condition who were treated with other regimens. Thus, the prevalence of complications is unknown. Still, the authors concluded that the sublingual use of nifedipine should be abandoned. We do not believe that the existing evidence supports such a strong conclusion, although it is probably true that the drug is given too commonly. Clinicians should also be aware that the U.S. Food and Drug Administration has not approved nifedipine for hypertensive emergencies.

The clinician faced with a patient must ask, Is this a true hypertensive emergency-one in which blood pressure is high and end-organ compromise exists? If the answer is yes, then nifedipine, given under monitored conditions, may be a reasonable choice. However, other agents, such as nitroprusside or labetolol, are more predictably useful. Each has its limitations-increased cyanide levels with nitroprusside and the general risks of ß-blockade with labetolol.

Conclusion

Top Conclusion Author & Article Info References

The major advances for the clinician caring for patients with renal disease have come in the area of improved understanding of pharmacologic and dietary therapy for progressive renal diseases, especially diabetic nephropathy. The central role of renin-angiotensin blockade in delaying or preventing renal failure has been further corroborated. Use of large databases to determine risk factors for renal dysfunction is an important trend that should lead to more rational selection of drug treatments, such as NSAID therapy. In the months before hemodialysis begins, better assessment of the need for anemia correction and more attention to the preservation of vascular access sites would strongly affect the survival and quality of life of patients with end-stage renal disease.

Dr. Henrich: Department of Internal Medicine, Medical College of Ohio, 13000 Arlington Avenue, Toledo, OH 43614.

Dr. Roberts (Series Editor): Madrona Medical Group, 4370 Cordata Parkway, Bellingham, WA 98226-8075.