María A. Azancot

Early treatment with eculizumab in atypical haemolytic uraemic syndrome

Atypical haemolytic uraemic syndrome (aHUS) is a rare and life-threatening disease caused by complement system dysregulation leading to uncontrolled complement activation and thrombotic microangiopathy. We report the case of an adult patient with plasmaphaeresis-resistant aHUS and hypertension treated with the complement inhibitor eculizumab. Eculizumab was shown to completely inhibit haemolysis, normalize thrombocyte levels and increase diuresis. Full recovery of renal function was not possible due to irreversible renal damage prior to eculizumab initiation. These findings highlight the importance of early treatment with eculizumab in patients with poor response to standard therapy, in order to avoid irreversible renal damage.

Hypertension in chronic kidney disease: the influence of renal transplantation.

Background Hypertension is one of the most prevalent cardiovascular risk factors in chronic kidney disease (CKD) and kidney transplants. The contribution of transplantation to hypertension in comparison to patients with CKD and similar renal function has not been characterized. Methods Ninety-two transplants and 97 CKD patients with an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 not receiving dialysis were enrolled. At entry, office blood pressure (BP) and 24-hr ambulatory blood pressure monitoring (ABPM) were obtained. Results Office BP was not different between transplants and CKD patients (139.5±14.3 vs. 135.2±19.3, P=1.00, respectively). ABPM 24-hr systolic blood pressure (SBP) (133.9±14.3 vs. 126.2±16.1, P=0.014), awake SBP (135.6±15.2 vs. 128.7±16.2, P=0.042), and sleep SBP (131.2±16.2 vs. 120.2 ±17.9, P=0.0014) were higher in renal transplants. When patients were classified according to BP patterns associated with highest cardiovascular risk, the proportion of patients with both nocturnal hypertension and non-dipper pattern was higher in transplants (68.5% vs. 47.4%, P=0.03). In the multivariate regression analysis, transplantation was an independent predictor of 24-hr, awake, and sleep SBP. Conclusion Office BP is similar in kidney transplants and CKD patients with similar renal function. On the contrary, hypertension is more severe in kidney transplants when evaluated with ABPM mainly as a result of increased sleep systolic BP. Thus, precise evaluation of hypertension in kidney transplants requires ABPM.

Inflammation and Atherosclerosis Are Associated With Hypertension in Kidney Transplant Recipients.

The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age‐matched patients with chronic kidney disease without history of cardiovascular events. Twenty‐four–hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log‐transformed interleukin 6 (Log IL‐6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty‐four–hour systolic blood pressure (SBP) (P=.0001), Log IL‐6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24‐hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL‐6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.

Múltiples quistes parapiélicos en la enfermedad de Fabry

Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis.

Tacrolimus and mycophenolate regimen and subclinical tubulo-interstitial inflammation in low immunological risk renal transplants

The aim was to evaluate the relationship between maintenance immunosuppression, subclinical tubulo‐interstitial inflammation and interstitial fibrosis/tubular atrophy (IF/TA) in surveillance biopsies performed in low immunological risk renal transplants at two transplant centers. The Barcelona cohort consisted of 109 early and 66 late biopsies in patients receiving high tacrolimus (TAC‐C0 target at 1‐year 6–10 ng/ml) and reduced MMF dose (500 mg bid at 1‐year). The Oslo cohort consisted of 262 early and 237 late biopsies performed in patients treated with low TAC‐C0 (target 3–7 ng/ml) and standard MMF dose (750 mg bid). Subclinical inflammation, adjusted for confounders, was associated with low TAC‐C0 in the early (OR: 0.75, 95% CI: 0.61–0.92; P = 0.006) and late biopsies (OR: 0.69, 95% CI: 0.50–0.95; P = 0.023) from Barcelona. In the Oslo cohort, it was associated with low MMF in early biopsies (OR: 0.90, 95% CI: 0.83–0.98; P = 0.0101) and with low TAC‐C0 in late biopsies (OR: 0.77, 95% CI: 0.61–0.97; P = 0.0286). MMF dose was significantly reduced in Oslo between early and late biopsies. IF/TA was not associated with TAC‐C0 or MMF dose in the multivariate analysis. Our data suggest that in TAC‐ and MMF‐based regimens, TAC‐C0 levels are associated with subclinical inflammation in patients receiving reduced MMF dose.

Histological findings in two renal transplants accomplishing operational tolerance criteria

Operational tolerance is defined as stable renal function in transplants without immunosuppression for at least 1 year. We present histological assessments of two patients with operational tolerance. The first withdrew immunosuppression in 2005 and presents stable renal function (creatinine 1.5 mg/dL) without proteinuria. The biopsy showed mild chronic tubulointerstitial changes without inflammation. The second withdrew immunosuppression in 2009 and maintains stable renal function (creatinine 1.6 mg/dL) with mild proteinuria. Histology showed chronic humoural rejection and Class II anti-human leukocyte antigen antibodies were detected. These cases suggest that a renal biopsy may be useful to rule out subclinical pathology in patients with operational tolerance.