Hyperuricemia and chronic kidney disease: an enigma yet to be solved.

The role of uric acid (UA) on the pathogenesis and progression of chronic kidney disease (CKD) remains controversial. Experimental and clinical studies indicate that UA is associated with several risk factors of CKD including diabetes, hypertension, oxidative stress, and inflammation and hyperuricemia could be considered as a common dominator linking CKD and cardiovascular disease. Notably, the impact of serum UA levels on the survival of CKD, dialysis patients, and renal transplant recipients is also a matter of debate, as there are conflicting results from clinical studies. At present, there is no definite data whether UA is causal, compensatory, coincidental or it is only an epiphenomenon in these patients. In this article, we attempt to review and elucidate the dark side of this old molecule in CKD and renal transplantation.

Salvage of a totally occluded peritoneal dialysis catheter by laparoscopic milking.

Mechanical problems of the Peritoneal Dialysis (PD) catheter remain a significant cause of temporary or even permanent transfer to hemodialysis. Until recently, the most popular approach was to remove the problematic PD catheter than to try to salvage it. We report a case of severe (two-way) PD catheter obstruction that appeared after spontaneous hemoperitoneum and did not resolve with multiple conservative measures. However, it was successfully salvaged by laparoscopic surgery and milking of a big intraluminal clot.

Sodium removal and peritoneal dialysis modalities: no differences with optimal prescription of icodextrin.

Continuous ambulatory peritoneal dialysis (CAPD) has been considered as a more efficient modality for sodium removal than automated peritoneal dialysis (APD), due to the longer dwell times and the sodium sieving phenomenon. However, because studies regarding sodium removal in peritoneal dialysis (PD) report rather controversial results and carry various methodological flaws, it remains uncertain whether they offer enough significant information regarding PD prescription and therapy. The aim of the present observational cross-sectional study was to evaluate the impact of the optimal prescription of CAPD and APD, regarding solute clearances and daily ultrafiltrate, on daily sodium removal. Forty-six (46) patients aged 52.3 ± 14 years were studied. Twenty-six (26) patients were subjected to CAPD, and 20 patients were subjected to APD. Ten (10) patients per group were prescribed icodextrin for the long dwell to achieve optimal adequacy and ultrafiltration (UF) targets. CAPD patients removed a higher, albeit not statistically significant, daily amount of sodium (131.7 ± 98.2 mmol) compared with APD patients (79.4 ± 129.2 mmol). Their Kt/V urea was lower (1.48 ± 0.3 vs. 2.17 ± 0.33, P < 0.05), and there were no differences on daily UF (1119 ± 533 vs. 1005 ± 517 mL). In both groups, icodextrin use for the long dwell resulted in equal sodium removal with that of patients not prescribed icodextrin. Our results, derived from an unselected PD population, indicate that although classic CAPD may be more efficient for sodium removal than APD, the use of icodextrin as an adjuvant for higher daily UF not only increases solute clearance but also removes more sodium for both modalities. In addition, calculations of sodium removal in PD do not seem to benefit the everyday clinical practice, provided that PD patients can achieve the adequacy targets and present optimal daily UF without signs of volume overload.

Different immunosuppressive combinations on T-cell regulation in renal transplant recipients.

BACKGROUND/AIMS: Recent studies indicate that regulatory T-cells (Tregs) promote transplant tolerance. We studied Treg levels in 39 stable renal transplant recipients to determine the sizes of the Treg populations and the effects of treatment regimens thereof. METHODS: All patients (19 with good graft function and 20 with chronic allograft nephropathy) received induction therapy (basiliximab) and were on triple immunosuppressive regimens with calcineurin inhibitors (cyclosporine or tacrolimus), mycophenolate mofetil (MMF) or everolimus and steroids. Twenty healthy subjects served as controls. Whole blood samples were stained with anti-CD4, CD25, CD127, and FoxP3 antibodies and analyzed by flow cytometry to determine CD4+CD25(high)FoxP3+/- and CD4+ CD25(high)CD127(-/low) Treg levels. RESULTS: All patients had significantly reduced CD4+CD25(high)FoxP3+/- but no CD4+ CD25(high)CD127(-/low) Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25(high)Foxp3+ Tregs and tacrolimus levels and CD4+CD25(high)Foxp3- Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25(high)Foxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors. CONCLUSION: Overall, immunosuppression lowers CD4+CD25(high)FoxP3+/- Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25(high)FoxP3+ Tregs, a fact that may influence long-term allograft survival.

Intermittent peritoneal dialysis (IPD): an old but still effective modality for severely disabled ESRD patients.

BACKGROUND: Hospital-based intermittent peritoneal dialysis (IPD) is an old PD modality applied for as long as 40 h per week using high volumes of PD fluid, but it has almost been abandoned due to its low solute clearances. However, IPD might be the only option for elderly dialysis patients with significant comorbidities, unable to undergo haemodialysis (HD) or PD at home without any assistance, for various reasons. METHODS: We describe our experience with 25 patients aged 71.2 +/- 7.5 years with a previous history of HD for 55.4 +/- 54 months, dialysed with IPD for more than 3 months. IPD was performed three times weekly for 8-10 h. RESULTS: Mean values for haematocrit, serum urea, creatinine, sodium, potassium and calcium were comparable with other ESRD populations, whereas there were significantly lower values for albumin (3.2 +/- 0.3 mg/dL) and significantly higher values for phosphorus (7.1 +/- 1.7 mg/dL) despite the use of phosphate binders. The patients survived for a mean of 16.8 +/- 11.5 (3-43) months despite very low solute clearances, as expressed by Kt/V urea (1 +/- 0.26) and weekly creatinine clearance (27.2 +/- 7.6 L/week). However, by using 22.9 +/- 4.5 L of various combinations of isotonic and hypertonic PD fluids, the mean ultrafiltrate was 1854 +/- 326 mL per session. There were only two cases of peritonitis, unrelated to IPD per se. CONCLUSIONS: Considering the underlying comorbidities, IPD remains a valuable and effective option with acceptable survival rates, for a special population of ESRD patients not able for various reasons to undergo HD, neither PD at home.

Sodium removal in peritoneal dialysis: the role of icodextrin and peritoneal dialysis modalities.

One of the main goals of dialysis is the control of extracellular volume, because inadequate sodium and fluid removal result in fluid overload and increased mortality. In the present study, we evaluated the roles of continuous ambulatory peritoneal dialysis (CAPD), continuous cycling peritoneal dialysis (CCPD), and the use of icodextrin on sodium removal in 29 patients (n = 18 on CAPD, n = 11 on CCPD). Daily removal of sodium by each modality and dialysis adequacy by Kt/V and creatinine clearance were evaluated. A significantly higher amount of sodium was removed in CAPD patients than in CCPD patients, although peritoneal dialysis clearances were lower in CAPD, and no difference in daily ultrafiltration was observed between the modalities. In the CAPD group, patients using icodextrin for the long dwell showed significantly increased 24-hour sodium removal (218 +/- 65 mmol/L) as compared with patients not using icodextrin (96.3 +/- 58 mmol/L, p < 0.001); they also showed increased daily ultrafiltration (1685 +/- 302 mL vs. 717 +/- 440 mL, p < 0.001). In the CCPD group, 8 patients were using icodextrin for the long dwell, and they showed significantly increased sodium removal only for the day exchange (43 +/- 49 mmol/L) as compared with patients not using icodextrin (-60 +/- 6, p < 0.001). Hypertension was less common in the CAPD patients than in the CCPD patients. These results indicate that CAPD is a more efficient modality than CCPD for sodium removal. Icodextrin is an effective tool not only for increasing adequacy, but also for removing more sodium in both modalities.

Peritonitis during the first year after commencement of peritoneal dialysis has an impact on technique survival and patient morbidity.

The timing of the first episode of peritonitis in peritoneal dialysis (PD) might have some special characteristics and may depend on many factors such as a patient's attitudes, age, comorbidity, or training capacity. It may also have a significant impact on further peritonitis episodes and technique failure. We retrospectively analyzed data for 168 PD patients who were undergoing continuous ambulatory PD by a twin-bag system, automated PD, or in-center intermittent PD over 12 years. There were 121 cases of peritonitis recorded in 60 patients, with an overall peritonitis rate of 1 episode per 45.75 patient-months. The mean time to the first episode of peritonitis after commencement of PD was 26.4 +/- 22 months (range: 1-110 months). In 20 patients, a first peritonitis episode presented rather early--during the first 12 months on PD (group A)--and in 27 patients, a first episode presented rather late-after at least 24 months on PD (group B). Group A had lower technique survival (30.4 +/- 26.5 months), were more prone to further episodes of peritonitis during follow-up, and had a total peritonitis rate of 1 episode per 14.85 patient-months. In group B, technique survival was longer (69.3 +/- 33.8 months), and the total peritonitis rate was 1 episode per 45.68 patient-months. We observed no differences between the two groups in comorbidity, age, or PD modality. These results indicate that patients with early-onset peritonitis are prone to making mistakes during connection, resulting usually in infection with gram-positive pathogens. These patients may present repeated peritonitis episodes and experience decreased technique survival.

Acid-base profile and predictors of metabolic acidosis in patients undergoing peritoneal dialysis with lactate- and bicarbonate-buffered peritoneal dialysis solutions.

Metabolic acidosis correction is one of the goals of renal replacement therapy. Correction of acidosis in peritoneal dialysis (PD) may be affected by PD modalities such as automated PD (APD) or by new solutions containing a combination of bicarbonate and lactate as a buffer [bicarbonate continuous ambulatory PD (CAPD)]. The aim of the present study was to examine the acid-base status of our PD population and to compare the effects of APD, lactate CAPD, and bicarbonate CAPD on serum bicarbonate levels. We studied 35 stable patients undergoing APD (n = 15), lactate-buffered (35 mEq/L) CAPD (n = 14), and bicarbonate/lactate-buffered CAPD (n = 6) for 48.5 +/- 38.1 months. Most of our patients had serum bicarbonate levels in the normal range. In 3 patients (8%), HCO3 was below 22 mEq/L, and in 8 patients (22%; APD = 2, lactate CAPD = 2, bicarbonate CAPD = 4), HCO3 was above 28 mEq/L. We found no statistically significant correlations between HCO3 serum levels and PD prescription, peritoneal membrane characteristics, or intake of calcium carbonate and sevelamer hydrochloride. Patients on bicarbonate CAPD had higher HCO3 serum levels, but this difference disappeared when corrections for duration of dialysis, residual urine volume, and PD adequacy indices were applied. In the studied PD population, adequate correction of metabolic acidosis was achieved, as reflected in serum bicarbonate levels. We observed no difference in serum bicarbonate levels between APD and lactate CAPD patients. The new bicarbonate-buffered PD solutions are more biocompatible and can result in higher serum bicarbonate levels. However, a significant number of PD patients on bicarbonate-buffered solutions may become alkalotic. The clinical significance of these results needs further examination in prospective studies.

Design, implementation and preliminary evaluation of a telemedicine system for home haemodialysis.

A telemedicine system for home haemodialysis was designed using a systems approach and a feedback model to produce the hardware and software specifications. Preliminary clinical trials at four European locations involved 29 patients and 305 sessions of haemodialysis. The evaluation included an evaluability assessment and formative evaluation. Central to the methodology was the detailed specification of a stakeholder/evaluation criterion matrix. Preliminary results indicated that the telemedicine system was capable of satisfying the requirements of formative evaluation as a precursor to evaluating its overall worth.

Transplant options for patients with type 2 diabetes and chronic kidney disease.

Chronic kidney disease (CKD) has become a real epidemic around the world, mainly due to ageing and diabetic nephropathy. Although diabetic nephropathy due to type 1 diabetes mellitus (T1DM) has been studied more extensively, the vast majority of the diabetic CKD patients suffer from type 2 diabetes mellitus (T2DM). Renal transplantation has been established as a first line treatment for diabetic nephropathy unless there are major contraindications and provides not only a better quality of life, but also a significant survival advantage over dialysis. However, T2DM patients are less likely to be referred for renal transplantation as they are usually older, obese and present significant comorbidities. As pre-emptive renal transplantation presents a clear survival advantage over dialysis, all T2DM patients with CKD should be referred for early evaluation by a transplant center. The transplant center should have enough time in order to examine their eligibility focusing on special issues related with diabetic nephropathy and explore the best options for each patient. Living donor kidney transplantation should always be considered as the first line treatment. Otherwise, the patient should be listed for deceased donor kidney transplantation. Recent progress in transplantation medicine has improved the "transplant menu" for T2DM patients with diabetic nephropathy and there is an ongoing discussion about the place of simultaneous pancreas kidney (SPK) transplantation in well selected patients. The initial hesitations about the different pathophysiology of T2DM have been forgotten due to the almost similar short- and long-term results with T1DM patients. However, there is still a long way and a lot of ethical and logistical issues before establishing SPK transplantation as an ordinary treatment for T2DM patients. In addition recent advances in bariatric surgery may offer new options for severely obese T2DM patients with CKD. Nevertheless, the existing data for T2DM patients with advanced CKD are rather scarce and bariatric surgery should not be considered as a cure for diabetic nephropathy, but only as a bridge for renal transplantation.

Prevalence of anemia in patients with type II diabetes and mild to moderate chronic kidney disease and the impact of anti-RAS medications.

Anemia is a common feature of diabetes and chronic kidney disease (CKD) mainly due to erythropoietin (EPO) deficiency and uremic toxicity. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been established as first-choice medications for the treatment of diabetic nephropathy. However, there are conflicting data regarding their impact on hemoglobin levels in patients with diabetic nephropathy. We evaluated the prevalence of anemia in 101 patients with diabetes mellitus type II and CKD at stage III-IV (group A) compared with 101 non-diabetic patients with similar renal function (group B). Moreover, we evaluated the impact of ACE inhibitors and ARBs on patients' anemia. Anemia was observed in 60 patients in group A and in 47 patients in group B (P < 0.01). Thirty-one (31) patients in group A and 19 patients in group B were receiving exogenous EPO for correction of renal anemia (P <0.05). Mean values of hemoglobin did not show significant differences (12.5 ± 1.8 vs 12.6 ± 1.7 g/dL) between the two groups. Seventy-five patients in group A and 52 patients in group B were receiving ACE inhibitors and/or ARBs (P <0.01), but, after multivariate analysis, we could not detect any association between anemia and the prescription of these medications. Anemia is more common in diabetic patients with CKD stage III-IV than in non-diabetic patients with similar renal function. Our results indicate that ACE inhibitors and ARBs are not a significant cause of anemia for both populations.