Manuel Macía

Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease: The PREDIAN Trial

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m(2) in the PTF group compared with 6.5±0.4 ml/min per 1.73 m(2) in the control group, with a between-group difference of 4.3 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m(2); P<0.001) in favor of PTF. The proportion of patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m(2) per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P<0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, -0.3% to 11.1%) in the control group and -14.9% (95% CI, -20.4% to -9.4%) in the PTF group (P=0.001). Urine TNF-α decreased from a median 16 ng/g (interquartile range, 11-20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2-18.4 ng/g) in the PTF group (P<0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria.

Relationship between serum magnesium and parathyroid hormone levels in hemodialysis patients

Acute magnesium (Mg) infusion decreases patathyroid hormone (PTH) secretion. However, the effect of chronic hypermagnesemia on PTH levels in dialysis patients is not well established. We studied 110 hemodialysis patients (mean age, 55 +/- 14 years; time on dialysis, 35 +/- 28 months) not receiving vitamin D and undergoing dialysis with an Mg dialysate concentration of 1.2 mg/dL. The primary phosphate binder was calcium carbonate, and 43% of the patients also needed aluminum hydroxide. During a 6-month period, calcium (Ca), phosphorus (P), and total serum Mg were measured every 2 months; intact PTH and aluminum (Al) were measured every 6 months. The mean value of each parameter was computed. Hypermagnesemia (serum Mg > 2.47 mg/dL) was observed in 73% of the patients. Mg and Ca were inversely correlated with PTH levels (r = -0.48; P < 0.001 and r = -0.21; P < 0.05, respectively). After adjusting for Ca and P (partial correlation analysis), Mg and PTH were inversely correlated (r = -0.58; P < 0.001). A stepwise multiple regression analysis showed that PTH levels were predicted by Mg (P < 0.001), alkaline phosphatase (P < 0.01), and P levels (P< 0.05; multiple R = 0.57; P < 0.001), whereas Ca level, sex (dummy variable), diabetes (dummy variable), time on dialysis, and Al level were not predictive. Patients with inadequately low PTH levels (relative hypoparathyroidism, PTH < 120 pg/mL; n = 52) showed greater serum Mg concentrations than the rest (n = 58; 3.01 +/- 0.33 v 2.63 +/- 0.38 mg/dL; P < 0.001). In conclusion, serum Mg concentrations in dialysis patients are independently associated with PTH levels, suggesting that chronic hypermagnesemia may decrease PTH secretion and/or synthesis. In addition, chronic hypermagnesemia of dialysis patients may have a role in the pathogenesis of adynamic bone disease.

Efficacy of molecular adsorbent recirculating system for the treatment of intractable pruritus in cholestasis

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Clinical evolution of post-transplant diabetes mellitus

BACKGROUND The long-term clinical evolution of prediabetes and post-transplant diabetes mellitus (PTDM) is unknown. METHODS We analysed, in this cohort study, the reversibility, stability and progression of PTDM and prediabetes in 672 patients using repeated oral glucose tolerance tests (OGTTs) for ≤5 years. RESULTS Most patients were on tacrolimus, steroids and mycophenolate. About half developed either PTDM or prediabetes. The incidence of PTDM was 32% and bimodal: early PTDM (≤3 months) and late PTDM. Early PTDM reverted in 31%; late PTDM developed in patients with post-transplant prediabetes. The use of OGTTs was necessary to detect around half of PTDM. Pretransplant obesity was a major risk factor for early PTDM, for its persistence and for late PTDM {odds ratio [OR] 1.18 [95% confidence interval (CI) 1.09-1.28]}. At 3 months, higher HbA1c promoted [OR 2.37 (95% CI 1.38-4.06)], while insulin sensitivity protected against [OR 0.64 (95% CI 0.48-0.86)] late PTDM. At 3 months, 28% had prediabetes; of these, 36% remained stable, 43% normalized and 21% developed late PTDM. Pretransplant obesity [OR 1.20 (95% CI 1.04-1.39)] and higher HbA1c [OR 3.80 (95% CI 1.45-9.94)] at 3 months promoted while insulin sensitivity protected against [OR 0.57 (95% CI 0.34-0.95)] evolution from prediabetes to late PTDM. Immunosuppressive levels or acute rejection did not influence PTDM. Most (84%) of the patients with normal tests at 3 months remained stable without evolving into PTDM; 14% developed prediabetes. CONCLUSIONS PTDM and prediabetes are very common in renal transplantation. Classic metabolic factors like obesity, prediabetes and insulin resistance promote the evolution of PTDM and prediabetes. Patients with normal glucose metabolism rarely develop PTDM. OGTT is necessary to detect PTDM and prediabetes and thus should be included in clinical practice.

Erdheim-Chester disease as cause of end-stage renal failure: a case report and review of the literature

Erdheim-Chester disease (ECD) is a rare, systemic, nonfamilial histiocytic disorder, first described by Jakob Erdheim and William Chester in 1930. Infiltration of histiocytes produces a xanthogranulomatous tissue deposit in many organs, including skin, lungs, bones, kidneys, retro-orbital and periorbital tissues, pituitary-hypothalamic axis, heart, great vessels, breast, skeletal muscle, central nervous system, sinonasal mucosa and retroperitoneum [1–4]. The development of fibrosis in the retroperitoneal area could compromise the urinary tract, especially middle and distal ureters and produce an obstructive renal disease if they are bilaterally affected [5–7]. This is a characteristic of ECD in contrast with retroperitoneal fibrosis which usually affects pelvic ureters. Bone pain is the most common presenting symptom, and characteristic radiographic changes in the long bones (bilateral cortical sclerosis, predominantly involving the metaphyses and diaphyses) are considered virtually pathognomonic. These changes can be suggested by Technetium-99 (Tc) bone scintigraphy, showing a symmetric and abnormally increased uptake, predominantly in the metadiaphyseal regions of the long bones. In any case, diagnosis should be confirmed by a tissue biopsy showing histiocytes without typical Langerhans cells characteristics. In ECD, electron microscopy does not reveal Birbeck granules and in immunohistochemical studies CD1a was uniformly negative in all cases of ECD reported to date and the lesional cells are usually S-100 negative, although positivity has been described in previous cases in the literature and in different organs in patients with otherwise typical disease [2]. In this report, we describe a case of ECD as cause of renal failure, and relevant literature is reviewed. For this, we performed a MEDLINE (National Library of Medicine, Bethesda, MD) search for ECD of all papers published until December 2009.

Eculizumab in secondary atypical haemolytic uraemic syndrome

Background. Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods. We identified 29 patients with so‐called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 109/L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results. Twenty‐nine patients with secondary aHUS (15 drug‐induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer‐related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow‐up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion. Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA‐inducing condition.

Should we adjust erythropoiesis-stimulating agent dosage to postdialysis hemoglobin levels? A pilot study

BackgroundPredialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requeriments. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE).MethodsCohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialysis Hb is proposed. During 18 months follow-up, CVE, hospitalizations and mortality were collected.ResultsAfter dialysis, Hb cocentration rise by 6.1 ± 5.6%. Using postdialysis Hb, the weight-adjusted ESA dosage would be lower respect to the prescription using predialysis Hb: 104 ± 120 vs 128 ± 124 U/kg/week (P < 0.001). Using predialysis Hb, 40.2% of subjects had a Hb level above 12 g/dL, whereas this percent increased to 70.1% using postdialysis Hb. During the follow-up, 15 patients had a CVE, without differences in Hb levels respect to subjects without CVE. However, patients with CVE had received higher ESA doses: 186 ± 180 vs 111 ± 98 U/Kg/week (P = 0.001). The prediction model is: Postdialysis Hb (g/dL) = 1.636 + 0.871 x predialysis Hb* (g/dL) + 0.099 x UF rate** (mL/kg/h) - 0.39 for women***. [R2 = 0.74; *P < 0,001; **P = 0.001; ***P = 0.03).ConclusionsPostdialysis Hb can be a better reflect of the real Hb level in hemodialysis patients. Using postdialysis Hb would avoid the use of inappropriately high ESA doses. The prediction of postdialysis Hb with an adjusted model would help us to identify those patients at risk for ESA overdosification.