Visceral leishmaniasis in adults with nephropathy.

The aim of this study is to evaluate the features of visceral leishmaniasis (VL) in adults with nephropathy, who were not infected with the human immunodeficiency virus. This is a retrospective study of 14 adults hospitalized between 2000 and 2014, with VL and renal involvement. Clinical, biological, and therapeutic data were collected from the patients' medical files. Eleven women and three men, most of whom were from the North of the country, with a mean age of 40.5 years were studied. Lupus was present in five cases, the Sicca syndrome in three cases, diabetes in one case, renal failure on dialysis in two cases, and there were three renal transplant recipients. Major clinical symptoms were fever and weakness in all cases. Enlargement of the spleen was present in eight cases and hepatomegaly in six cases. Biologic inflammatory syndrome and anemia were present in all cases, and pancytopenia was present in seven cases. Renal insufficiency was noted in all cases. Diagnosis of VL was confirmed by bone marrow examination or serology. Treatment consisted of antimoniate in 10 cases and amphotericin B in four cases. Seven deaths were recorded. Clinical symptoms of VL are atypical in patients with nephropathy and therefore, the diagnosis should be suspected in such patients because VL is still endemic in our country.

Cyclosporine therapy in steroid-dependent or steroid-resistant idiopathic focal and segmental glomerulosclerosis.

Focal and segmental glomerulosclerosis (FSGS) is a heterogeneous entity. Previous few studies have evaluated the efficacy of calcineurin inhibitors in primary FSGS and have suggested positive benefit. In this single-center, retrospective study (1975-2014), we report our experience in Tunisian adults with primary FSGS treated with cyclosporine A (CsA). It includes patients histologically proven FSGS and managed in the Charles Nicolle Hospital at Tunis, Tunisia. The dose of CsA was adjusted to maintain a whole blood trough level of 80-150 ng/mL. The observation period was 6.8 ± 3.7 years after CsA treatment. Twenty-three patients with idiopathic FSGS, treated with CsA, were studied. The mean age was 26.69 ± 10.1 years, and the sex ratio was 2.83. Eight patients (35%) had a steroid-dependent nephrotic syndrome (NS), and 15 patients (65%) had for steroid-resistant NS. After a median follow-up of 16.5 months on CsA, we noticed complete remission of the NS in eight cases (35%) after 12.12 ± 8 months, partial remission in five (22%) after 3 ± 0.7 months, dose-dependent remission to CsA (2.87 mg/kg/day) in four (17%), and a no response in six patients (26%). Eleven patients (48%) showed improvement of renal function, while eight (35%) developed end-stage renal disease (ESRD) after 35.7 ± 20.9 months. Predictive factors of progression to ESRD were creatinine clearance <90 mL/min before introduction of CsA (P = 0.0054) and CsA-resistance (P = 0.053). Our study suggests that CsA is effective in the treatment of patients with idiopathic FSGS. Initial renal function and cyclosporineresistance are the predictive factors of ESRD in steroid-resistant or -dependent FSGS.

Renal impairment in multiple myeloma: A single center experience.

To determine the features of the different forms of kidney diseases associated with multiple myeloma (MM), we retrospectively studied 144 patients with kidney injury and MM at our institute from 1974 to 2014. The mean age of the patients was 60.1 years and the male:female ratio was 1.25. Renal disease was concomitant with the discovery of MM in 92% of cases. The mean follow-up of our patients was 2.1 years. Initial renal insufficiency was found in 131 (91%) patients. Cast nephropathy of the distal tubule was found in 110 (26%) patients, renal amyloidosis in 16 (11.1%), and light chain deposition disease in five (3.47%). Twelve (8.3%) patients had chronic glomerular nephropathy. Twenty-six patients reached end-stage renal failure within 13.4 months. Renal survival was 30.45 months. Predictive factors for improvement of renal function undergoing chemotherapy included serum creatinine <250 µmol/L, proteinuria <1 g/24 h, and the non-use of renal replacement therapy. Multiple pathogenic mechanisms can contribute to kidney injury in myeloma patients. Novel myeloma agents have shown considerable promise in reversing renal failure in some patients and improving outcomes.

Allograft renal rejection and chemokine polymorphism.

Chemokines play a major role in the process by which leukocytes are recruited from the bloodstream into the sites of inflammation. Genes for the chemokine receptors CCR5, CCR2 and MCP-1 are characterized by functional polymorphisms implicated in transplant rejection. To investigate this association, we analyzed polymorphisms of CCR5-∆32, CCR5-59029-A/G, CCR2-V64I and MCP-1 G/A (-2518) in 173 renal transplant recipients and 169 healthy blood donors. The patients were classified in two groups: Group-1 (G-1) included 33 HLA-identical recipients and Group-2 (G-2) included 140 (one or more) mismatched graft recipients. Forty-two patients had developed acute rejection episodes (ARs): seven in G-1 and 35 in G-2. Thirteen G-2 patients developed chronic allograft dysfunction (CAD). The genotypic and allelic frequencies of all polymorphisms studied did not reveal significant differences between patients and controls and among G-1 and G-2 recipients. However, a significant risk of acute renal transplant rejection was found in G-1 patients who possessed the CCR2-64I allele (odds ratio 0.24, 95% confidence inter-val [CI], 0.05-1.06; P = 0.035). There was no significant association of this polymorphism and CAD. In conclusion, the observed association of CCR2-64I with AR should be added to the spectrum of immunogenetic factors known to be involved in allograft renal loss.

Dissecting aortic aneurysm in maintenance hemodialysis patients.

The dissecting aortic aneurysm (DAA) is a rare pathology that may result in fatal outcome. We report follow up of three cases of DAA patients undergoing maintenance hemo-dialysis who were managed conservatively.

Gastrointestinal angiodysplasia in chronic renal failure.

Gastrointestinal (GI) hemorrhage is a frequent and sometimes life-threatening complication of end-stage renal failure. Angiodysplasia (AD), vascular malformation, is the most common cause of recurrent lower-intestinal hemorrhage in patients with renal failure. We report four chronic hemodialysis patients with AD. All patients presented with severe anemia requiring transfusion. GI hemorrhage ceased spontaneously in three cases and after treatment with argon plasma coagulation in another. Diagnosis of AD is usually challenging, since its cause is still unknown, and its clinical presentation is variable. Lesions are multiple in 40-75% of cases, often located in the stomach and duodenum but can affect the colon and the jejunum. Diagnosis is improved by endoscopy which has a much higher sensitivity compared to angiography. Capsular endoscopy may reveal the hemorrhage site in the small intestine when regular endoscopy fails, and therapeutic intervention usually include argon plasma coagulation.

Ctla-4 exon 1 (+49) and promoter (-318) gene polymorphisms in kidney transplantation.

To investigate the association between kidney transplant rejection and the polymorphisms of CTLA-4 gene exon 1(+49) and promoter (-318), genomic DNA of 70 renal transplant recipients and 110 healthy blood donors were genotyped by PCR-RFLP and PCR-SSP, respectively. The patients were classified in two groups: G1 included 33 HLA-identical recipients and G2, 37 one haplo-identical recipients. Thirty-one recipients experienced an acute rejection episode: 10 in G1 and 21 in G2. Ten G2 patients developed chronic allograft dysfunction (CAD). Allelic frequencies and genotype distribution were similar among patients and controls. CTLA-4 exon 1 genotype A/A and CTLA-4 promoter genotype C/C were significantly higher among G2 patients with CAD than without CAD (P < .01). The distribution of CTLA-4 exon 1-promoter genes did not reach significance between graft recipients and controls. The genotype frequency of (G/G-C/C) was increased among controls (42.72%) compared with graft recipients (G1 and G2; 35.71%). CTLA-4 polymorphisms gene were associated with susceptibility to chronic allograft dysfunction.

Comparison of HLA Class I and II Molecular and Serological Typing within Clinical Laboratory.

In order to develop an adequate tissue typing strategy, we performed human leukocyte antigen (HLA)-A, B and DR generic typing on 235 (120 HLA-A, B and 115 HLA-DR) routine clinical samples by polymerase -chain reaction (PCR)-SSP in parallel with conventional serological typing. At the A locus, there were two (1.7%) discrepancies between molecular and serological typing besides 25 (20.8%) serological blanks, which was defined by molecular typing. At the B locus, there were two (1.7%) discrepancies and 30 serological blanks, which were defined by molecular typing. At the DR locus there were two (1.8%) discrepancies and 44 serological blanks, which were defined by molecular typing. We conclude that molecular typing is of substantial benefit in the resolution of poorly defined serological antigens. In view of the low percentage of discrepancy between the serological and molecular typing besides the high cost of molecular typing, our policy is to perform HLA typing first by the serological method and to use PCR-SSP as an adjuvant tool.

Visceral leishmaniasis in a patient with sicca syndrome and nephropathy.

A 63-year-old woman presented with severe volume depletion and pre-renal azotemia. She had xerostomia, xerophthalmia and cervical lymhadenopathy. Urine examination revealed proteinuria, hematuria and glycosuria. Laboratory studies, after volume repletion, revealed hyper-gammaglobulinemia. Renal biopsy showed interstitial nephropathy and salivary-gland biopsy showed glandular atrophy and diffuse fibrosis. Diagnosis of leishmaniasis was established by bone marrow examination and serology. The patient was treated with pentavalent antimonial (Glucantime) with an excellent response. The treatment, however, had to be interrupted because of transient nephrotoxicity. After a break of four weeks, the antimonial was reinstituted with no more side effects. Both the sicca syndrome and the nephropathy responded very well to the treatment at nine months follow-up. In this case the presentation of visceral leishmaniasis was atypical, probably because of the partially suppressed immunity. The clue to the diagnosis was the polyclonal hypergammaglobulinemia.