Walter Douthat

CKD-EPI instead of MDRD for candidates to kidney donation.

Background The determination of the glomerular filtration rate (GFR) is critical for the selection of a potential kidney donor. The complex and impractical techniques for the measurement of GFR have led to the development of equations to estimate GFR. Modification of diet in renal disease (MDRD) formula is the most widely used but its performance is poor because it systematically underestimates GFR above 60 mL/min. A new formula called the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) seems to overcome this limitation but needs to be tested in healthy potential kidney donors. Methods From 2007 to 2011, a cross-sectional study was performed on 85 adults who were candidates for living-related kidney donation. GFR was measured by nonradiolabeled iothalamate clearance determined by high-performance liquid chromatography, and renal function was estimated by using CKD-EPI and MDRD equations. The overall performance of the equations was analyzed, and the estimation for GFR above 90 mL/min was studied by means of receiver operating characteristic curves. Results The mean (SD) (range) of the measured GFR was 116 (24) (64–160) mL/min per 1.73 m2, estimated GFR with CKD-EPI was 108 (22) (64–153) mL/min per 1.73 m2, and MDRD was 99 (28) (46–157) mL/min per 1.73 m2. CKD-EPI presented lower bias (3.3 vs. 10.2 mL/min/1.73 m2), higher precision [interquartile range (minimum value-maximum value), 25 (53–140) vs. 32 (43–161) ml/min] and higher accuracy (100% vs. 89%) compared with MDRD. Conclusion The CKD-EPI equation showed a higher performance than the MDRD equation in the GFR estimation of healthy population. CKD-EPI is applicable instead of MDRD, to subjects or candidates for kidney donation to avoid wrong GFR underestimates, which may lead to an inappropriate exclusion of candidates.

High-dose steroid treatment increases free water transport in peritoneal dialysis patients

The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore that mediates free water transport during peritoneal dialysis (PD). Proof-of-principle studies performed in rats have shown that treatment with corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries, causing a significant increase in free water transport. Whether such a beneficial effect could be observed in end-stage renal disease patients treated by PD remains unknown. Peritoneal transport parameters were evaluated in three patients on PD, shortly before and after living-donor renal transplantation and treatment with high-dose methylprednisolone (1.0-1.2 g/m(2)). As compared with pre-transplantation values, the post-transplantation test revealed an ∼2-fold increase in the sodium sieving and ultrasmall pore ultrafiltration volume, suggesting an effect on AQP1 water channels. In contrast, there was no change in the parameters of small solute transport. The direct involvement of AQP1 in these changes is suggested by the expression of glucocorticoid receptors in the human peritoneum and the presence of conserved glucocorticoid response elements in the promoter of the human AQP1 gene.

Percutaneous ethanol injection therapy in post-transplant patients with secondary hyperparathyroidism

Persistent hyperparathyroidism is frequent in postrenal transplant patients. Percutaneous ethanol injection therapy (PEIT) is an alternative for treatment of patients with secondary hyperparathyroidism but it was not described in postrenal transplant patients. We report our experience with PEIT to control hyperparathyroidism in the post‐transplant period. We performed PEIT under ultrasonographic guidance and local anesthesia in eight patients because of persistent secondary hyperparathyroidism after renal transplantation. Indications for PEIT were: high intact parathyroid hormone (iPTH) levels with hypercalcemia, hypophosphatemia, osteopenia and/or bone pain. All patients had at least one visible parathyroid nodule by ultrasonography. Biochemical assays were performed immediately before PEIT, between 1 and 7 days after last PEIT, and a mean of 8.0 ± 2.8 months after PEIT. Serum iPTH and calcium levels decreased significantly after treatment and remained unchanged until final control. Serum iPTH decreased from 286.9 ± 107.2 to 154.6 ± 42.2 pg/ml (P < 0.01) after PEIT (percentual reduction 36.5 ± 9.5%). This response was significantly correlated to total ethanol volume used (r: 0.94, P < 0.0001). Hypercalcemia disappeared in six of eight patients treated. Only minor complications were registered. There were no changes in renal function related to the treatment. Our findings show that PEIT is a useful and safe alternative for patients with persistent post‐transplant secondary hyperparathyroidism.

Use of Percutaneous Ethanol Injection Therapy for Recurrent Secondary Hyperparathyroidism after Subtotal Parathyroidectomy

We evaluated the efficacy of percutaneous ethanol injection therapy (PEIT) as a therapeutic option for recurrence of secondary hyperparathyroidism after subtotal parathyroidectomy in ESRD patients. Six patients underwent PEIT. A mean of 1.3 ± 0.8 ethanol injections was performed. Nodular volume was 1.5 ± 1.7 cm3, and 2.8 ± 2.8 cm3 of ethanol was injected per patient. After ethanol injection PTH decreased significantly (1897 ± 754 to 549 ± 863 pg/mL (P < .01)). There was also a reduction in serum calcium, phosphorus and calcium-phosphorus product. A positive and significant correlation was found between nodular volume with ethanol injected and time from parathyroidectomy. Only one patient required hospitalization due to severe hypocalcaemia. In other two cases, local discomfort and temporary mild dysphonia were registered. PEIT is an effective treatment to control recurrences of secondary hyperparathyroidism postsubtotal parathyroidectomy.

New options for the management of hyperparathyroidism after renal transplantation.

The persistence and severity of hyperparathyroidism (HPT) post-renal transplantation is relatively frequent and primarily associated with the timing and its magnitude in the pre-transplant period and with the presence of parathyroid adenomas. HPT after renal transplantation is clinically manifested with hypercalcemia, hypophosphatemia, bone pain, fractures, and in more serious cases with cardiovascular calcifications that affect the survival. The primary clinical objective for patients with secondary HPT after renal transplantation is to obtain a level of parathyroid hormone (PTH) adequate to the renal transplanted function and to normalize levels of calcium, phosphorus and vitamin D. In many cases during this period, the development of hypercalcemia and/or hypophosphatemia makes it necessary to take different therapeutic measures. The use of vitamin D or its analogues has been extrapolated from the management of pre-transplant HPT obtaining variable outcomes, although its use is limited by its capacity to produce hypercalcemia. Calcimimetics are drugs that have proven be effective in reducing PTH levels in patients with HPT on dialysis and has been effective in reducing up to 50% PTH levels in moderate to severe HPT in post-renal transplantation.When HPT persists after renal transplantation and does not respond to medical treatment, invasive management by percutaneous ethanol injection therapy of parathyroid glands or parathyroidectomy should be considered. The emergence of new methods for the management of HPT expands the availability of therapeutic tools for transplant patients.

Elevada prevalencia de hiperparatiroidismo secundario en pacientes con enfermedad renal crónica en diálisis en Argentina

BACKGROUND There are few data in Argentina on the prevalence and management of bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD). OBJECTIVES AND METHODS A survey was carried out in dialysis units in 2010 to measure the prevalence of and types of treatments for BMM disorders in Argentina. The data obtained was then compared to the published results from other large population studies. We recorded characteristics of dialysis centres and participating patients, the frequency of measurements and individual results for BMM biochemical markers, as well as the type of management used to control hyperphosphataemia and secondary hyperparathyroidism. RESULTS 1210 patients from 25 dialysis centres in Argentina participated in the study (representing 4.7% of the country’s prevalent dialysis population in 2010). The mean patient age was 55.3±17.6 years, 60.8% were male, 3.3% were on peritoneal dialysis and 29.1% suffered diabetes. In all centres, phosphataemia and calcaemia were measured on a monthly basis, 60% of centres measured intact parathyroid hormone (iPTH) every 6 months, 36% every 3 to 4 months, and 4% annually. As recommended by K/DOQI, 51.6% of patients had adequate levels of calcium (8.4-9.5 mg/dl), 51.6% had adequate phosphorus (3.5-5.5 mg/dl) and 21.1% displayed acceptable iPTH levels (150-300 pg/ml). 24% had iPTH <150 pg/ml and 54.5% >300 pg/ml. iPTH ≥600 pg/ml was present in 28.3%, and 13.3% had values ≥1000 pg/ml. These figures differed from those published by the DOPPS II study, in which 51.1% of patients had iPTH <150 pg/ml, and only 26.7% had iPTH ≥300 pg/ml. Calcium-based phosphate binders were used in 83.6% of the patients, 5.6% used sevelamer and 4.0% used aluminium-containing compounds. To achieve control of hyperparathyroidism, oral or intravenous calcitriol was predominantly used (50.5%) with a small percentage of patients receiving paricalcitol or doxercalciferol. CONCLUSIONS The present study shows a high prevalence of secondary hyperparathyroidism, which differs from that published by other large population studies. There was a high proportion of patients with BMM markers outside the ranges suggested by K/DOQI. Mainly phosphate binders based on calcium and calcitriol continue to be used for the management of hyperphosphatemia and hyperparathyroidism respectively.

Renal transplantation in high cardiovascular risk patients

Current transplant success allows recipients with previous contraindications to transplant to have access to this procedure with more frequency and safety. The concept of high-risk patient has changed since the first stages of transplantation. In the first studies, the high-risk concept was based on probability of early graft failure or on a patients clinical condition to cope with high perioperatory morbimortality. Later on, this concept implied immunological factors that were crucial to ensure transplant success because hypersensitized or polytransfused patients experienced a higher risk of acute rejection and subsequent graft loss. Afterward, the presence of various comorbidities would redefine the high-risk concept for renal transplant mainly considering recipients clinical aspects. Currently, the change in epidemiological characteristics of patients starting dialysis causes that we now deal with a greater increase of elderly patients, diabetic patients, and patients with history of cardiovascular disease. Today, high-risk patients are those with clinical features that predict an increase in the risk of perioperative morbimortality or death with functioning graft. In this review, we will attempted to analyze currents results of renal transplant outcomes in terms of patients and graft survival in elderly patients, diabetic patients, and patients with previous cardiovascular disease from the most recent experiences in the literature and from experiences in our center. In any of the groups previously analyzed, survival offered by renal transplant is significantly higher compared to dialysis. Besides, these patients are the recipient group that benefit the most with the transplant because their mortality while remaining on dialysis is extremely high. Hence, renal transplantation should be offered more frequently to older patients, diabetic patients, and patients with pretransplant cardiac and peripheral vascular disease. A positive attitude toward renal transplantation is needed by physicians taking care of these patients from predialysis stages of chronic renal failure.

Expanded criteria donors, histological scoring, and prolonged cold ischemia: impact on renal graft survival.

The use of expanded donors or kidneys with preexistent chronic damage remains controversial, but they offer the opportunity to expand the donor pool. We investigated the impact of these conditions as predictors of graft survival among a cohort of recipients with prolonged cold ischemia times and a high incidence of delayed graft function. We included 70 consecutive cadaveric kidney allografts implanted between 2001 and 2005, which had undergone an early graft biopsy. Delayed graft function was present in 84% of cases with moderate or severe preexistent chronic damage in 63% and 27% of biopsies, respectively, and acute rejection was diagnosed in 14.3% of overall cases. The graft survival was 73.3% at 48 months. Primary nonfunctioning kidneys were more frequent using kidneys from expanded compared with standard donors (20.0% vs 0.0%, P < .002). Multivariate analysis showed that only the donor condition (standard vs expanded) was independently associated with graft survival (hazard ratio: 0.12; 95% confidence interval: 0.01-0.87; P < .03). Our results suggested that the donor characteristics prevail over other variables to predict graft outcomes.

Thrombophilic Mutations: No Association With Thrombotic Events in Renal Transplant Recipients

Factor V Leiden and mutation of prothrombin gene G20210A have been associated with poor results in the early post-kidney transplantation period. Its long-term importance in stable patients has yet to be evaluated. We studied the prevalence of these inherited mutations and their relationship to thrombotic events in 82 Argentine renal transplant recipients with adequate long-term kidney function. In aggregate, 7.2% of patients were carriers of these mutations; however, their presence did not show any association with thrombotic events or renal function alterations. The routine evaluation for these mutations does not seem to be cost-effective in renal transplant patients.

Hydrocele Caused by Peritoneal Fluid Leakage Through Inguinal Canal

C. parapsilosis infection again, whereas biopsy samples from the omentum revealed inflammatory changes, foci of liponecrosis, and fungal spores consistent with Candida (Figure 2). Due to unresolved infection (persistent fever and elevated white blood cell (WBC) and CRP levels for 12 days after admission), fluconazole was substituted for caspofungin. Serial blood cultures were persistently negative. Infection signs persisted for a further 7 days. Antifungal therapy was continued for 1 month. The patient was finally discharged in good clinical condition and is currently being treated with hemodialysis. The case presents some remarkable points. First, fungal peritonitis usually occurs with predisposing factors, such as prolonged use of antibiotics and previous bacterial peritonitis (1). Surprisingly, our patient had no predisposing factors. Secondly, inflammatory signs and symptoms may persist for weeks despite appropriate antifungal treatment and early catheter removal, especially for Candida parapsilosis cases (2,3). Finally, intraoperative findings of erythematous plaques, characteristic of fungal infection, are the definitive proof of the diagnosis. To our knowledge, no similar images of C. parapsilosis peritonitis have been published in the literature.