The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury. We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks. All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period. Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease.

Overhydration and sarcopenia, related to an individual’s nutritional status, have been associated with increased cardiovascular mortality and poor prognosis in patients on hemodialysis. The purpose of this study was to investigate the prediction of overhydration and sarcopenia on mortality in patients on hemodialysis using a body composition monitor. We conducted a systematic review and meta-analysis using a random-effects model. We searched the Cochrane Central Register, OVID MEDLINE, EMBASE and PubMed databases for all studies published prior to December 9, 2016 and reviewed the reference lists of relevant reviews, registered trials and relevant conference proceedings. The overhydration group (fluid excess, >15% vs. the normohydration group) and the low lean tissue index group ( <10%) were compared with a reference group. Six trials, consisting of 29,469 patients, were included in the pooled analysis. The pooled hazard ratio for overall survival of the overhydration group, compared with the reference normohydration group was 1.798 (95% confidence interval [CI]: 1.53–2.804, p = .001). The hazard ratio for mortality in the low lean tissue index group was 1.533 (95% CI, 1.411–1.644; p = .001) in the random-effects model. The results from the most recent study showed the greatest heterogeneity in the sensitivity analysis. Low lean tissue index and overhydration, measured using a body composition monitor, were associated with a high mortality rate in patients on hemodialysis.

Seun Deuk Hwang, Jin Ho Lee, Jong Hyun Jhee, Joon Ho Song, Joong Kyung Kim, Seoung Woo Lee. Kidney Res Clin Pract 1999;0:. https://doi.org/10.23876/j.krcp.18.0106

Despite the renoprotective effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), many patients with chronic kidney disease develop end-stage kidney disease. Combination treatment with an ACEI and an ARB is a recently introduced approach to obtain more complete blockade of the renin–angiotensin system, based on the different mechanisms of action of the two classes of drug. To assess the shortcomings of single treatment with ACEIs and ARBs, and the potential benefits of combination treatment, we reviewed the experimental and clinical evidence suggesting that combination treatment offers more complete blockade of the renin–angiotensin system and identified areas in which further research is necessary to confirm the benefits of combination treatment. The available data suggest that combination treatment with an ACEI and an ARB has a greater renoprotective effect than either drug alone. In addition, more recent data have shown that combination treatment is more potent in suppressing renal fibrosis, and is well tolerated in patients with advanced chronic kidney disease. Clinical trials with rigorous endpoints are needed to further establish the benefits of combination treatment in renal protection.