Costas Fourtounas

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+CD25highFoxP3± and CD4+ CD25highCD127–/low Treg levels. Results:All patients had significantly reduced CD4+CD25highFoxP3± but no CD4+ CD25highCD127–/low Treg levels compared to controls. Renal allograft function did not correlate with Treg levels. Statistically significant correlations between CD4+CD25highFoxp3+ Tregs and tacrolimus levels and CD4+CD25highFoxp3– Tregs and HLA-DR mismatching were detected. Patients receiving MMF had significantly higher CD4+CD25highFoxp3+ Tregs compared to patients on everolimus who were also receiving lower doses of calcineurin inhibitors. Conclusion:Overall, immunosuppression lowers CD4+CD25highFoxP3± Treg levels significantly in the periphery in renal transplant recipients. In addition, different immunosuppressive regimens have different impacts on CD4+CD25highFoxP3+ Tregs, a fact that may influence long-term allograft survival.

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.

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 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.

Eosinophilic Peritonitis Following Air Entrapment During Peritoneoscopic Insertion of Peritoneal Dialysis Catheters

Eosinophilic peritonitis following peritoneal dialysis catheter insertion is an infrequent but important complication. While allergic reaction to catheter material has been noted to be a culprit, air infusion into the abdominal cavity has also been highlighted to be a cause of this complication. In this article, we report two patients with end‐stage renal disease where air entrapment in the peritoneal cavity during a peritoneal dialysis catheter insertion resulted in eosinophilic peritonitis. The complication resolved with the reabsorption of entrapped intraperitoneal air and treatment with ketotifen. Peritonitis observed in the postoperative period during the peritoneoscopic insertion of a peritoneal dialysis catheter could be the result of air entrapment. Such patients might not require antibiotic therapy or catheter removal. Reabsorption of entrapped air and treatment with ketotifen might be all that is required.

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.”

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.

Gingival Hyperplasia and Calcium Channel Blockers

To the Editor: We read with interest the case report of Tajani and Nesbitt regarding severe gingival hyperplasia (GH) in a hypertensive patient who had received multiple calcium channel blockers (CCBs). The problem of GH with CCBs, although well established in the literature, has not been studied in depth in hypertensive patients, possibly due to the multiple options for alternative classes of antihypertensive medications. In renal transplant recipients, the combination of cyclosporine as an antirejection agent, especially with CCBs as antihypertensives, may result in GH in a significant number of patients. The options for these patients are (1) to convert immunosuppression from cyclosporine to tacrolimus or (2) to stop CCBs, although the second option may not fully reduce GH. However, after the initial report by Wahlstrom and colleagues, there have been many reports regarding the beneficial role of azithromycin, a macrolide antibiotic, which can reverse or accelerate the recovery from GH in renal transplant recipients who are using cyclosporine and CCBs. This is true even for a case of severe GH described by Tajani and Nesbitt. We have used this medication with success in renal transplant recipients. We have also treated 3 hypertensive patients with GH induced by CCBs (nifedipine, amlodipine, and verapamil) with a short regimen of azithromycin (250 mg for 3 days). These patients were intolerant to other classes of antihypertensives, or they were well controlled by CCBs and did not wish to change them. No patient presented with any side effects, and the improvement in GH was apparent after 2 to 3 weeks. In one patient with severe GH, a second course was given after 1 month in order to achieve full GH regression. Thus, in hypertensive patients with GH, a trial with azithromycin might be of value before discontinuing CCBs and before initiation of any dental surgical interventions.—Costas Fourtounas, MD, PhD; Jannis G. Vlachojannis, MD, PhD Department of Internal Medicine-Nephrology, Patras University Hospital, Patras-Greece

Kidney, Pancreas and Islet Transplant Options for Patients with Diabetic Nephropathy

Recent progress in surgery and immunosuppression has expanded the “transplant menu” for patients with diabetic nephropathy which is now including: Kidney Transplantation from a Deceased Donor (DDKT) or a Living Donor (LDKT), Simultaneous Pancreas Kidney (SPK), Pancreas Transplantation Alone (PTA), Pancreas after Kidney (PAK) and Islet transplantation. As pre-emptive transplantation presents a clear survival advantage over dialysis, all diabetic patients with chronic kidney disease (CKD) should be referred for early evaluation by a transplant center. For type 1 diabetes mellitus (T1DM) patients, LDKT and SPK transplantation offer superior and approximately equivalent long-term patient and allograft survival. PAK transplant rates tend to decline due to surgical and immunological complications, but it may still be considered for well selected candidates with preserved kidney allograft function. For type 2 diabetes mellitus (T2DM) patients, not only LDKT, but even DDKT are superior to dialysis. SPK transplantation should be offered only in selected cases with special metabolic characteristics similar to T1DM. PTA should be considered only for selected cases of T1DM with well preserved renal function (eGFR>80 ml/min/1.73 m2 and minimal proteinuria), as it may a cause of rapid deterioration of renal function. Islet transplantation should still be considered as an experimental procedure for T1DM, and has no place in patients with advanced CKD, but it may be applied in already immunosuppressed patients following KT. However, the best transplant option for patients with diabetic nephropathy therapy should always be individualized, taking under consideration the patients’ preferences and expectations, their overall medical condition and the transplant center’s experience with all these procedures.