Therapeutic modalities in diabetic nephropathy: standard and emerging approaches.

Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, proteinuria/albuminuria reduction, interruption of the renin-angiotensin-aldosterone system through the use of angiotensin converting enzyme inhibitors and angiotensin type-1 receptor blockers, along with dietary modification and cholesterol lowering agents. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are urgently needed. This review highlights the available standard therapeutic approaches to manage progressive diabetic nephropathy, including markers for early diagnosis of diabetic nephropathy. Furthermore, we will discuss emerging strategies such as PPAR-gamma agonists, Endothelin blockers, vitamin D activation and inflammation modulation. Finally, we will summarize the recommendations of these interventions for the primary care practitioner.

Effect of renin-angiotensin-aldosterone system blockade therapy on incidence of contrast-induced nephropathy in patients with chronic kidney disease.

INTRODUCTION: The incidence of contrast-induced nephropathy (CIN) ranges between 10% and 50% among high-risk patients. Whether medications that affect rennin-angiotensin-aldosterone system (RAAS) have any impact on the development of CIN remains uncertain. MATERIALS AND METHODS: We performed a retrospective study of patients with CKD stages 3 and 4 who were either on or off RAAS blockade therapy at the time of coronary angiography. Development of CIN was defined by a 25% increase of serum creatinine from baseline or an increase in serum creatinine by 0.5 mg/dL from baseline. Serum creatinine values were recorded before contrast exposure and for 5 days after coronary angiography. RESULTS: A total of 178 patients with CKD who had coronary angiography during the study period were included, of whom 62 (35%) were on ACE inhibitors, 12 (7%) were on ARBs, and 1 (1%) was on combination of ACE inhibitors and ARBs. The estimated glomerular filtration rate was 44.0 ± 11.5 mL/min. The odds ratio of acute kidney failure on day 5 was 0.73 (95% confidence interval, 0.31 to 1.69) for the ACE inhibitors and 0.46 (95% confidence interval, 0.06 to 3.70) for ARBs. Multivariable analysis revealed the findings to be independent of demographic variables, comorbidities, type of contrast medium, and the prophylactic strategies. CONCLUSIONS: Patients on RAAS blockade therapy before contrast exposure did not have an increased incidence of CIN. There was also no increased incidence of CIN with ACE inhibitors or ARBs in the subgroups at higher risk, such as those with diabetes mellitus.

Impact of computerized order entry and pre-mixed dialysis solutions for continuous veno-venous hemodiafiltration on selection of therapy for acute renal failure.

To investigate the impacts of availability of pre-mixed solutions and computerized order entry on nephrologists' choice of the initial mode of renal replacement therapy in acute renal failure. We studied 898 patients with acute renal failure in 3 consecutive eras: era 1 (custom-mixed solution; n = 309), era 2 (pre-mixed commercial solution; n = 324), and era 3 (post-computerized order entry; n = 265). The proportion of patients treated with renal replacement therapy and the time from consult to initiation of continuous renal replacement therapy was similar in the 3 eras. Following introduction of the pre-mixed solution, the proportion of patients treated with continuous renal replacement therapy increased (20% vs. 33%; p < 0.05), it was initiated at a lower serum creatinine (353 ± 123 µmol/L vs. 300 ± 80 µmol/L; p < 0.05) and in older patients (53 ± 12 vs. 61 ± 14 years; p < 0.05). There was a progressive increase in the use of continuous veno-venous hemodialysis (18% vs. 79% vs. 100%; p < 0.05) and in the total prescribed flow rate (1,382 ± 546 vs. 2,324 ± 737 vs. 2,900 ± 305 mL/hr 3; p < 0.05). There was no significant impact on mortality. The availability of a pre-mixed solution increases the likelihood of initiating continuous renal replacement therapy in acute renal failure, initiating it at a lower creatinine and for older patients, use of continuous veno-venous hemodialysis and higher prescribed continuous renal replacement therapy dose. Computerized order entry implementation is associated with an additional increase in the use of continuous veno-venous hemodialysis, higher total prescribed dialysis dose, and use of CRRT among an increasing number of patients not on mechanical ventilation. The effect of these changes on patient survival is not significant.