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.

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.

Hypomagnesemia, chronic kidney disease and cardiovascular mortality: pronounced association but unproven causation.

Magnesium is as an essential metal implicated in numerous physiological functions of human cells. The kidney plays a crucial role in magnesium homeostasis. In advanced chronic kidney disease, serum magnesium levels are increased. Data from experimental and observational studies suggest that low levels of magnesium are associated with several factors, such as insulin resistance, diabetes, oxidative stress, hypertension, atherosclerosis, and inflammation which are implicated in the progression of chronic kidney disease. Moreover, low levels of magnesium have been correlated with cardiovascular disease and all-cause mortality in end-stage renal disease patients. Hypomagnesemia has also been associated with poorer renal allograft and transplant recipients' outcomes. The causality of these relationships has not been completely elucidated. A thorough review of the current literature indicates that low magnesium levels in dialysis patients may reflect a poorer nutritional status and/or are the result of systemic inflammation. Further studies in chronic kidney disease and dialysis patients are needed in order to clarify the causality of these associations.

The thyroid and the kidney: a complex interplay in health and disease.

Thyroid hormones may directly affect the kidney and altered kidney function may also contribute to thyroid disorders. The renal manifestations of thyroid disorders are based on hemodynamic alterations or/and to direct effects of thyroid hormones. The renin-angiotensin system plays a crucial role in the cross-talk between the thyroid and the kidney. Hypothyroidism may be accompanied by an increase of serum creatinine and reduction of glomerular filtration rate (GFR), whereas hyperthyroidism may increase GFR. Treatment of thyroid disorders may lead to normalization of GFR. Primary and subclinical hypothyroidism and low triiodothyronine (T3) syndrome are common features in patients with chronic kidney disease (CKD). In addition low levels of thyroid hormones may predict a higher risk of cardiovascular and overall mortality in patients with end-stage renal disease. The causal nature of this correlation remains uncertain. In this review, special emphasis is given to the thyroid pathophysiology, its impact on kidney function and CKD and the interpretation of laboratorial findings of thyroid dysfunction in CKD.

Role of testosterone in the pathogenesis, progression, prognosis and comorbidity of men with chronic kidney disease.

Testosterone deficiency and hypogonadism are common conditions in men with chronic kidney disease (CKD). A disturbed hypothalamic-pituitary-gonadal axis due to CKD is thought to contribute to androgen deficiency. Data from experimental studies support the hypothesis that exogenous administration of testosterone may induce the activation of the renin-angiotensin system (RAS), the production of endothelin and the regulation of anti- or/and proinflammatory cytokines involved in the pathogenesis of hypertension and kidney damage. On the other hand, low testosterone levels in male patients with CKD are paradoxically associated with a higher risk of morbidity and mortality, possibly explained by anemia, osteoporosis and cardiovascular disease. In this article, we present an overview of clinical and experimental studies of the impact of testosterone on the progression and prognosis of male patients with CKD; even today, this remains a controversial issue.

Pathogenesis and management of intradialytic hypertension.

Hypertension is common in chronic kidney disease patients especially in those undergoing hemodialysis (HD). Usually, blood pressure falls after the HD session but in some patients a paradoxical increase has been observed during or immediately after HD. This phenomenon is referred as intradialytic hypertension. HD patients with intradialytic hypertension or increased blood pressure during HD present higher cardiovascular (CV) morbidity and mortality rates. The underlying mechanism of intradialytic hypertension is multifactorial. Activation both of renin-angiotensinaldosterone system (RAAS) and sympathetic nervous system, volume and sodium overload with concomitant increase in cardiac output, and endothelial dysfunction have been implicated in the pathogenesis of intradialytic hypertension. Given the lack of clinical trials regarding the pathophysiology and management of intradialytic hypertension, current treatment strategies are based mainly on experts' opinion. The purpose of this review is to describe the pathophysiology of intradialytic hypertension and discuss current strategies in order to improve intradialytic blood pressure management and concomitant HD patients' outcomes.

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.

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.

Diagnosis and management of chronic kidney disease in the elderly: a field of ongoing debate.

Chronic kidney disease (CKD) is rather common in elderly adults who comprise the fastest growing subset of patients with end-stage renal disease (ESRD). At present, there are no specific guidelines and recommendations regarding early identification and management of elderly with CKD and the current CKD classification system may overestimate its exact prevalence. Screening strategies based either in a more accurate formula of estimation of GFR alone, or preferably in combination with proteinuria are urgently needed in order to raise awareness and to promote early diagnosis of CKD in the elderly. The number of elderly dialysis patients is also increasing and may lead to severe socio-economic problems worldwide. Both hemodialysis and peritoneal dialysis can sustain life, but present various disadvantages. There is a trend for home based dialysis therapies but the results are based on a small number of patients. Recent reports indicate that dialysis may not provide a clear benefit over non-dialysis regarding survival and quality of life issues, especially in the presence of extensive comorbidities. Current practices around the world regarding access to dialysis in the elderly are rather controversial, reflecting each country's health policies and ethical patterns. Although advanced age should not be considered as an absolute contraindication for kidney transplantation, it is not frequently offered in elderly ESRD patients due to the shortage of renal grafts. Global judgment of all physical and mental/psychological issues and full informed consent regarding possible complications are mandatory before listing elderly ESRD patients for kidney transplantation. As scientific evidence is rather scarce, there is an urgent need for prospective studies and an individualized approach for the diagnosis and treatment of the elderly CKD patients, in order to optimize care and improve quality of life in this special population.

Delusional parasitosis: a rare cause of pruritus in hemodialysis patients.

Uremic pruritus is a common symptom in patients undergoing hemodialysis (HD) or peritoneal dialysis, but its exact pathogenesis remains rather unclear. However, severe or "intractable" pruritus may be the manifestation of another underlying disease or disorder other than uremia. Delusional parasitosis, or Ekbom syndrome, is a rare psychiatric disorder characterized by the false conviction of being infested with parasites, and it can be primary, or secondary to several medical and psychiatric disorders. We report 2 elderly HD patients who presented one after another, with delusional parasitosis. At some point in time, the delusional beliefs of the first patient were adopted by the second patient who was waiting to start his HD session on the same bed and HD machine, on a subsequent shift. They were both diagnosed with Ekbom syndrome and described as having monosymptomatic hypochondriac delusion. They were both prescribed antipsychotic medications. During follow-up they admitted feeling better than before; however, they remained concerned about the "insects/parasites."

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.