[End stage of chronic kidney disease and metabolic acidosis]. / Konecné stadium chronického onemocnení ledvin a metabolická acidóza.

Renal function disorder is inevitably associated with metabolic acidosis. An adult produces approximately 1 mmol of acids/kg of body weight every day (3 mmol/kg in children), derived from metabolization of proteins from food. Development of metabolic acidosis in patients with kidney disease is based on accumulation of acids and insufficient production of bicarbonates; alkaline loss represents a marginal issue here limited to patients with type II renal tubular acidosis only. The prevalence of this disorder increases with declining glomerular filtration (GFR) from 2% in patients with GFR 1.0-1.5 ml/s/1.73 m2 to 39% in patients with GFR < 0.3 ml/s/1.73 m2 or, alternatively, to 19% in patients with GFR 0.25-0.3 ml/s/1.73 m2. Notwithstanding the primary cause of the renal disease, declining GFR is associated with compensatory increase in ammoniac production in residual nephrons. This is an adaptive mechanism aimed at maintaining sufficient elimination of acids despite reduced volume of functional tissue. However, an increased ammoniac production simultaneously becomes a stimulus for activation of the complement via an alternative route and is thus one of the factors contributing, through this induced inflammation, to progression of tubular interstitial fibrosis that subsequently leads to further GFR reduction. Metabolic acidosis has a number of severe adverse effects on the organism, e.g. deterioration of kidney bone disease through stimulation of bone resorption and inhibition of bone formation, inhibition of vitamin D formation, increased muscle catabolism, reduced albumin production, glucose metabolism disorder, increased insulin resistance, reduced production of thyroid hormones, increased accumulation of ß2-microglobulin etc. Non-interventional studies suggest that alkali supplementation may slow down progression of chronic nephropathies. However, this approach, safe and inexpensive, has not been widely implemented in clinical practice yet. With respect to dialyzed patients, abnormal levels of bicarbonates are associated with increased mortality. Both metabolic acidosis and alkalosis, rather regularly seen in a considerable number of patients, have a negative effect on patient survival. Alkali substitution from a dialysis solution is the main pillar of metabolic acidosis management in patients on hemo- as well as peritoneal dialysis. Available technologies allow individualization of the treatment and this should be observed.

[Specific aspects of peritoneal dialysis in diabetic patients]. / Specifické aspekty peritoneální dialýzy u diabetiku.

Together with hemodialysis and renal transplantation, peritoneal dialysis is an established method of renal replacement therapy. While evolving in parallel with hemodialysis worldwide, it was not until 1990 that peritoneal dialysis, as we know it today, was introduced to this country when high-quality disposables also became available. In the early 1990s, after adequately increasing the throughput of our dialysis and transplant centers, renal replacement therapy became available to all patients requiring it, that is, also to those with diabetes and other patients with comorbidities in this country. The mortality rates of dialysis-dependent patients with diabetes and chronic renal failure are significantly higher compared with those of dialysis patients without diabetes. This holds true both for hemodialysis and peritoneal dialysis. The survival rates of dialysis patients (with and without diabetes) over the first years of dialysis treatment are higher for those on peritoneal dialysis compared with hemodialysis, presumably because residual renal function is maintained longer with peritoneal dialysis. Peritoneal dialysis in patients with diabetes is usually associated with a higher incidence of peritonitis, but not its complications. This is not the case in our unit where the incidence of peritonitis does not differ significantly between patients with diabetes (1 : 38.9 months) and those without it (1 : 51.4 months). However, peritonitis incidence in our center is kept at levels much lower than accepted by the European guidelines (1 : 24) and those developed by the International Society of Peritoneal Dialysis (1 : 18), and than is usual in current clinical practice. Peritoneal dialysis patients and, in particular, those with diabetes, are likely to benefit from the use of modern peritoneal dialysis solutions containing the glucose polymer icodextrin or amino acids as the osmotic agent instead of glucose, or dialysis solutions with a reduced content of glucose degradation products. Such solutions have been shown to feature improved biocompatibility parameters and lower systemic metabolic load. Some observational non-randomized trials have reported improved survival and a lower incidence of peritonitis in patients both with and without diabetes treated with these modern dialysis solutions. Randomized trials are warranted to confirm these findings.

Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation.

Both preemptive therapy and universal prophylaxis are used to prevent cytomegalovirus (CMV) disease after transplantation. Randomized trials comparing both strategies are sparse. Renal transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to 3-month prophylaxis with valacyclovir (2 g q.i.d., n = 34) or preemptive therapy with valganciclovir (900 mg b.i.d. for a minimum of 14 days, n = 36) for significant CMV DNAemia (>/=2000 copies/mL by quantitative PCR in whole blood) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. The 12-month incidence of CMV DNAemia was higher in the preemptive group (92% vs. 59%, p < 0.001) while the incidence of CMV disease was not different (6% vs. 9%, p = 0.567). The onset of CMV DNAemia was delayed in the valacyclovir group (37 +/- 22 vs. 187 +/- 110 days, p < 0.001). Significantly higher rate of biopsy-proven acute rejection during 12 months was observed in the preemptive group (36% vs. 15%, p = 0.034). The average CMV-associated costs per patient were $5525 and $2629 in preemptive therapy and valacyclovir, respectively (p < 0.001). However, assuming the cost of $60 per PCR test, there was no difference in overall costs. In conclusion, preemptive valganciclovir therapy and valacyclovir prophylaxis are equally effective in the prevention of CMV disease after renal transplantation.