[Severe recurrent intrahepatic cholestasis in systemic AL amyloidosis without obvious liver involvement: unexplained hepatic toxicity or a case of misdiagnosed liver amyloidosis?]. / Colestasi intraepatica in corso di amiloidosi sistemica AL senza evidenza istologica di un coinvolgimento epatico: un caso di epatopatia tossica o una mancata diagnosi di amiloidosi epatica?

We report the case of a 50-year-old woman who was admitted to the hospital for acute abdominal pain with nephrotic proteinuria, rapidly progressive renal failure, and moderate anemia. Laboratory tests showed mild Bence Jones (λ) proteinuria with negative serum immunofixation and a mild increase in λ free light chains. A bone marrow biopsy and a fat tissue aspirate showed multiple myeloma and amyloidosis. Because of the end-stage renal disease, the patient began regular dialysis treatment and was started on bortezomib 1.3 mg/m2 plus dexamethasone 40 mg on days 1, 4, 8 and 11 of 21-day cycles. Ten days later she complained of a new episode of abdominal pain with jaundice. A CT scan and an MRI scan ruled out all secondary causes of cholangitis including cancer. Acute intrahepatic cholestasis due to amyloid deposition was then hypothesized. After 4 well tolerated cycles of bortezomib and dexamethasone, blood tests showed a complete hematological response with full reversal of cholestasis. After three months, a new episode of abdominal pain occurred and this time the patient was operated on and found to have an intestinal volvulus. Because of the jaundice, a transjugular liver biopsy was performed showing no evidence of amyloid deposits. Two months later the patient died of septic shock. Although no autopsy was performed and the ultimate cause of the cholestasis could not be ascertained, amyloidosis remains the major culprit in this unfortunate case.

Conservative management of chronic kidney disease stage 5: role of angiotensin converting enzyme inhibitors.

BACKGROUND: Benefits and risks of angiotensin converting enzyme inhibitors (ACE-I) in advanced chronic kidney disease (CKD) are controversial. We tested the role of ACE-I in slowing the progression of renal damage in a real-world elderly population with CKD stage 5. METHODS: We evaluated all patients consecutively referred to our CKD stage 5 outpatient clinic from January 2002 to December 2013. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m2. We retrieved parameters of interest at baseline and assessed eGFR reduction rate during follow-up. We estimated GFR by the 4-variable Modification of Diet in Renal Disease (MDRD) formula. RESULTS: Mean age of the 342 subjects analyzed was 72 years and eGFR 10 ml/min/1.73 m2. In the 188 patients on ACE-I at baseline, the subsequent annual rate of eGFR reduction was less than a third of that found in the 154 patients off ACE-I. Across phosphate quartiles, baseline eGFR significantly decreased while its annual reduction rate significantly increased. Of the original cohort, 60 patients (17 %) died, 201 (59 %) started dialysis and 81 (24 %) were still in conservative treatment at the end of the study. Multivariate analysis identified age, phosphate, proteinuria, baseline eGFR and its rate of progression as independent risk factors directly or inversely predictive of progression to dialysis. ACE-I use significantly reduced by 31 % the risk of dialysis. CONCLUSIONS: Our study shows that proteinuria independently predicts further renal damage progression even in end-stage renal disease patients not yet in dialysis. In our cohort of elderly patients with very advanced CKD, ACE-I was effective in slowing down further renal damage progression.

[Free light chains reduction on acute kidney injury in multiple myeloma: critical role of high cut-off membranes]. / Il trattamento del danno renale acuto in corso di mieloma multiplo: ruolo della rimozione delle catene leggere libere con membrane ad elevato cut-off.

We report our experience with five patients, with dialysis dependent AKI and multiple myeloma (MM). Two of them were already suffering from a mild degree of renal insufficiency, one was on follow-up for smouldering MM and two had a relapse of symptomatic MM. Median concentration of the involved FLC (iFLC) was 15104 mg/L (range 1196-24384). All patients underwent three times per week HCO-HD for 6 hour sessions using Theralite 2100 (median 10, range 6-13 sessions) with one having further twelve sessions of 4 hours using SUPRA device (Bellco). In addition, they followed a bortezomib and dexamethasone regimen according to a bi-weekly schedule (3-5 cycles) plus Thalidomide. iFLC concentrations were measured by immunonephelometry in blood at the beginning of each dialysis session. All patients but one, showed a very good partial hematological response. The only exception demonstrated a partial response. iFLCs decreased between 72,8% and 99,7% in a median period of three weeks. After 6 months three patients underwent autologous stem-cell transplantation (ASCT), one of whom repeated the procedure 6 months later. In conclusion, three patients became dialysis independent at the end of the HCO-HD period, one patient became dialysis independent three months later and one remained dialysis dependent. Recovery of renal function in 4 out of 5 patients with a very good hematological response is a consequence of an early and fast removal of the iFLC joined to an efficient therapeutic regimen.

Relationship among endothelial response to hyperemia, bone marrow-derived progenitor cells, and parathyroid hormone in renal transplantation.

BACKGROUND: Endothelial dysfunction may contribute to modulate cardiovascular complications in renal transplant recipients (RTRs), and a relationship between endothelial dysfunction and parathyroid hormone (PTH) levels in RTRs has been demonstrated. We evaluated the relationship between endothelial response to hyperemia and circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) PTH, and genetic parameters in RTRs. METHODS: In 120 RTRs and in healthy subjects without (n=107, group A) and with cardiovascular risk factors (n=109, group B), we evaluated endothelial response to hyperemia through digital tonometry (peripheral arterial tonometry) detected by reactive hyperemia index (RHI) and EPCs and CPCs by flow cytometry. RESULTS: In RTRs, RHI median value was lower than in group A (P=0.05). EPC number was significantly lower in RTRs than in groups A and B (P<0.0001), whereas PTH median value was significantly higher (P<0.0001). In RTRs, RHI values were significantly lower according to the presence of three or more risk factors (P=0.04) and positively correlated with EPCs (P=0.04) but not with PTH (P=0.2). In patients who underwent dialysis for more than 5 years, lower RHI values (P=0.08), EPC number (P=0.5), and higher PTH concentrations (P=0.09) than in patients with less than 1 year dialysis time were observed. No relationship between eNOS gene -786T>C, 894G>T, and 4a/4b polymorphisms and RHI, EPC, and CPC number was found. CONCLUSIONS: This study shows an altered endothelial response, associated with reduced EPCs, and increased PTH in RTRs; the evaluation of endothelial status in RTRs may contribute to better assess the risk profile of these patients.

Can skin be the first site of CMV involvement preceding a systematic infection in a renal transplant recipient?

Cytomegalovirus (CMV) is an important and well-described opportunistic virus in renal transplant recipients (RTRs) with infection occurring mainly after the first month post-renal transplant. CMV can present as primary infection, reinfection or reactivation of latent disease. Skin manifestations are rare and variable, and diagnosis is often delayed. We present one case of skin CMV ulcer of perineal areas without systemic symptoms of CMV disease and a negative quantitative polymerase chain reaction. This case serves to illustrate the protean nature of CMV disease in RTR.

Successful treatment of refractory wart with a topical activated vitamin d in a renal transplant recipient.

Warts are benign proliferations of the skin and mucosa caused by infection with human papillomavirus. They are commonly treated with destructive modalities such as cryotherapy with liquid nitrogen, local injection of bleomycin, electrocoagulation, topical application of glutaraldehyde, and local and systemic interferon-ß therapy. These treatment modalities often cause pain and sometimes scarring or pigmentation after treatment. We herein report a case with a right index finger wart, which was successfully treated with a topical activated vitamin D.