[Renal involvement in sarcoidosis: Prognostic and predictive factors]. / Atteinte rénale au cours de la sarcoïdose : facteurs pronostiques et prédictifs.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease that primarily affects the respiratory system and lymphatic vessels. Renal involvement is rare, poorly studied and found in less than 10% of cases. The objective of our study was to identify factors of poor renal prognosis and predictive factors of renal involvement during sarcoidosis. METHODS: It's a retrospective study including patients hospitalized in our department for sarcoidosis with renal involvement over a period of 40 years. To study renal survival, we identified two groups of patients with renal manifestations of sarcoidosis by following their evolution: group A (n=26) represents those with renal remission or deterioration of renal function but without progression to end-stage renal disease and group B (n=8) those with progression to end-stage renal disease. To detect the predictive factors of end-stage renal disease in patients with sarcoidosis, we compared the clinical and paraclinical characteristics of our patients (group 1) to those of 44 patients with sarcoidosis without renal impairment followed in our department during the same period (group 2). RESULTS: Renal involvement was observed in 34 patients hospitalized for sarcoidosis (43.6%). There were 28 women and 6 men with a sex ratio of 0,21. The mean age at diagnosis of sarcoidosis was 47.1 years. The median time from sarcoidosis diagnosis to renal disease was 2 months (range 1-72). Tubulointerstitial nephropathy was the most frequent renal manifestation observed in 24 patients (70.6%). Hypercalcemia and hypercalciuria were found in 52.9% and 46.4% respectively. Renal failure was noted in 25 patients (73.5%). Corticosteroid therapy was initiated in 33 patients (97%) associated with immunosuppressive therapy in 3 cases. Predictive factors of end-stage renal disease were advanced age at diagnosis of nephropathy (P=0.007), comorbidities (P=0.002), multi-organ involvement (P=0.041), initial renal failure (P=0.013), interstitial fibrosis (P=0.006) and renal granulomas (P=0.007). Predictive factors of renal impairment during sarcoidosis were multi-organ involvement, inflammatory syndrome and hypercalcemia. CONCLUSION: Renal envolvement, although rare during sarcoidosis, can influence the prognosis hence the great interest of its early detection to prevent progression to end-stage renal failure.

Encapsulating Peritoneal Sclerosis after kidney Transplantation: Success of Medical Treatment.

Encapsulating peritoneal sclerosis (EPS) is an infrequent but serious complication of long-term peritoneal dialysis (PD). EPS may become clinically apparent when patients are on PD (classical EPS) or after undergoing kidney transplantation (post-transplantation EPS). This presentation of EPS seems to occur shortly after kidney transplantation in former PD patients. In this report, we present our experience in our first case of patient diagnosed with EPS after kidney transplantation.

New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene.

BACKGROUND: Karyomegalic interstitial nephritis (KIN) is a rare disease entity first described by Burry in 1974. The term KIN was introduced by Mihatsch et al. in 1979. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to a progressive decline of renal function. The prevalence of this disease is less than 1% of all biopsies, and its pathogenesis is unclear. KIN results from mutations in FAN1 (FANCD2/FANCI-Associated Nuclease 1), a gene involved in the DNA damage response pathway, particularly in the kidney. In this study, we report two Tunisian consanguineous families with KIN caused by mutations in the FAN1 gene. METHODS: Direct sequencing of the coding regions and flanking intronic sequences of the FAN1 gene was performed in three affected members. Three prediction programs (Polyphen-2 software, SIFT, and MutationTaster) were used to predict the functional effect of the detected variations. RESULTS: Two causative frameshift variants in the FAN1 gene were identified in each family: The previously described frameshift mutation c.2616delA (p.Asp873ThrfsTer17) and a novel mutation c.2603delT (p.Leu868ArgfsTer22) classified as "pathogenic" according to the American College of Medical Genetics and Genomics (ACMG) guidelines. CONCLUSION: To our best knowledge, this is the first Tunisian study involving familial cases of KIN with mutations in the FAN1 gene. We hypothesize that these findings can expand the mutational spectrum of KIN and provide valuable information on the genetic cause of KIN.

Deep vein thrombosis: An unusual way of revealing microscopic polyangiitis. Deep vein thrombosis in microscopic polyangiitis.

Unexplained deep vein thrombosis may justify screening for antineutrophil cytoplasmic antibody-associated vasculitis as it can be an unusual presentation of this disease.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits: Successful treatment for new and rare entity.

Proliferative glomerulonephritis with monoclonal immunoglobulin deposits is a new disorder with undefined treatment modalities. We propose cyclophosphamide-bortezomib-dexamethasone and autologous stem cell transplantation as a therapeutic protocol.

Renal Thrombotique microangiopathy: An unusual renal involvement in Niemann-Pick disease type B.

Renal involvement in Niemann-Pick disease type B is very rare. Kidney check-up and renal biopsy should be performed in any patient presented with hypertension and kidney disease. Histology identifies the lesion, the prognosis, and guide treatment.

Mycophenolate Mofetil-induced Oral Ulcerations in a Kidney Transplant Recipient.

INTRODUCTION: Mycophenolate Mofetil (MMF) is an immunosuppressive drug usually used in kidney transplants to prevent rejection. It has various adverse effects such as leucopenia, anemia, diarrhea but Mouth ulcers are rarely reported. METHOD: We present a case report of MMF-induced mouth ulcers in an African patient. CASE REPORT: A 41-year-old African-male patient has painful oral ulcers which developed 5 months after kidney transplantation. The immunosuppressive maintenance regimen comprised Steroids, Tacrolimus and MMF. RESULT: These ulcers were firstly related to a fungic or viral infection so the patient was prescribed Fluconazole and Aciclovir without any improvement. Then, Tacrolimus blood level was checked and it was in a therapeutic range. Finally, we decide to stop MMF and the ulcers healed quickly. DISCUSSION: Oral ulcers are frequently seen complications in immunosuppressant patient but are rarely described with MMF. These ulcers can become large and very painful and degrade patient's life quality. So when infections causes are excluded, we have to keep in mind that these ulcers can be a drug adverse effect.

Monoclonal gammopathy of renal significance with light-chain deposition disease in kidney transplantation.

Light-chain deposition disease (LCDD) reoccurs almost invariably after renal transplantation, leading to early graft loss. We report a case of LCDD with monoclonal gammopathy of renal significance diagnosed in the post-transplant period in a 28-year-old male and we discuss the diagnostic and therapeutic challenges in the clinical course.

Tubulointerstitial nephritis due to sarcoidosis: Clinical, laboratory, and histological features and outcome in a cohort of 24 patients.

Renal involvement is rare in systemic sarcoidosis. Among renal manifestations, tubulointerstitial nephritis (TIN) is the most commonly reported finding. We conducted the current study to investigate the clinical, laboratory, and histological features and to analyze the outcome of TIN due to sarcoidosis. We present a retrospective, single-center study of patients followed for sarcoidosis and presenting with TIN related to this systemic disease. Twenty-four patients were assessed (22 females/2 males). The mean age at diagnosis of TIN was 46.3 years. Extrarenal manifestations were dominated by thoracic involvement (95.8%), peripheral lymph nodes (54.2%), and skin lesions (33.3%). The mean proteinuria level was 0.68 g/24 h. Renal failure was diagnosed in 83.3% of cases with a median estimated glomerular filtration rate at 14.3 mL/min/1.73 m2. Nine patients presented with hypercalcemia and 12 patients with hypercalciuria. Renal biopsy was performed in 58.3% of cases. Six of the 14 patients presented with noncaseating granulomatous interstitial nephritis and eight with interstitial nephritis without granuloma. Granulomatous infiltration of renal parenchyma was complicated by vasculitis in two cases. Corticosteroid therapy was used in all patients. On follow-up analysis, four patients progressed to end-stage renal disease (ESRD) after a mean duration at 45.5 months. In the remaining patients, kidney function statistically significantly improved after one month of treatment compared to the time when the diagnosis was initially established (P = 0.031). We found that the predictive factors of progression to ESRD were multiorgan involvement (P = 0.032), advanced fibrosis F3 (P = 0.0006), and extensive interstitial granulomas (P = 0.007) and these were independently correlated with ESRD. Corticosteroid therapy seems to be effective in sarcoid TIN, but some degree of persistent renal failure is possible which can be predicted from both histologic findings and initial response to steroid therapy.

Simultaneous acute pancreatitis and angioedema associated with angiotensin-converting enzyme inhibitor.

Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed drugs for blood pressure (BP) control and renal protection. The use of ACEI is not associated with an increased risk of acute pancreatitis and ACEI-induced angioedema is rare. A 36-year-old woman presented with vomiting, headache, and aphasia. Her BP was 220/100 mm Hg. urine analysis revealed proteinuria (2+), hematuria (3+). Serum creatinine level was at 1125 µmol/L. She had anemia with 6.1 g/dL of hemoglobin and thrombocytopenia (61,000/mm3). Renal histology revealed lesions of thrombotic microangiopathy. The diagnosis of atypical hemolytic uremic syndrome was made by the complement factor I deficiency. Plasma exchanges could not be done. She was placed on peritoneal dialysis for renal insufficiency. We introduced an ACE (captopril) for the treatment of high BP. Twelve-hours after taking the first dose, she experienced severe epigastric pain and two episodes of vomiting. Serum lipase was 560 IU/L, and abdominal computed tomography showed Stage B pancreatitis. Twenty-four hours later, the patient developed marked edema of the neck region without dyspnea or dysphonia. Cervical ultrasound revealed the infiltration of the subcutaneous tissues. Captopril was stopped with the progressive disappearance of the edema. Serum lipase was 350 IU/L and then normalized at the end of the 4th day. Clinicians should be careful about widely used drugs and their side effects. ACEI can cause potentially life-threatening complications such as angioedema and acute pancreatitis. Possibly, there could be a common mechanism for the onset of pancreatitis and angioedema under ACEI.

Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of literature.

Secondary renal amyloidosis (RA) is the most common type of renal involvement in ankylosing spondylitis (AS). We assessed the epidemiologic and clinico-biological profile of AS patients with RA, to analyze treatment modalities and prognostic aspects, and to determine predictive factors of RA during AS. This was a retrospective study including 13 cases of RA among 212 cases who presented with AS, during the period from 1978 to 2006. The median age of the patients at the time of diagnosing AS was 47 years (range: 19-67). There were 11 males and two females. RA onset was diagnosed after a mean follow-up of 144.6 months (range: 10-505) from the AS diagnosis. We noted erosive peripheral arthritis, lumbar stiffness with bamboo spine, and coxitis in 23.1%, 76.9%, and 30.8% of cases, respectively. Nephrotic syndrome was found in eight patients (61.5%). At the time of diagnosing RA, six patients had renal failure. Amyloid deposits were histologically proven by salivary gland biopsy in six cases (46.1%) and by renal biopsy in seven cases (53.8%). Four patients received a long-course treatment with colchicine but with a good outcome only in two cases. In our series, AS was more severe among patients with RA. Four predictive factors of RA were identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo spine (P = 0.001), and biologic indicators of inflammation (P = 0.0001). High erythrocyte sedimentation rate was identified as the only independent risk factor of RA during AS (P = 0.0001). Renal function as well as urinalysis should be monitored at regular intervals to detect early renal involvement during AS.

Nondiabetic renal disease in patients with type 2 diabetes.

Diabetic nephropathy (DN) is one of the major complications of type 2 diabetes mellitus (T2DM). The diagnosis of DN is mostly clinical. Kidney biopsy is indicated only if nondiabetic renal disease (NDRD) is suspected. This study is aimed to assess the prevalence of NDRD and to determine predictor and prognostic factors of DN, NDRD. It was a retrospective analytic study including T2DM patients in whom renal biopsies were performed at our department from 1988 to 2014. Seventy-five patients were included. Mean age was 52.7 years with sex ratio at 1.56. Renal biopsy findings were isolated NDRD in 33 cases, NDRD superimposed on DN in 24 cases, and isolated DN in 18 cases. Most common NDRD found were focal segmental glomerulosclerosis (21%) and membranous nephropathy (19%). Multivariate analysis showed that the absence of ischemic heart disease [odds ratio (OR) = 0.178, 95% confidence interval (CI) = 0.041-0.762], absence of peripheral vascular disease (OR = 0.173, 95% CI = 0.045-0.669), and presence of hematuria (OR = 7.200, 95%CI = 0.886-58.531) were independent predictors of NDRD. 24 patients reached end-stage renal disease 55% in DN group, 16% in DN associated to NDRD group, and 30% in NDRD group. The prevalence of NDRD found in our study confirmed usefulness of renal biopsy in patients with T2DM, especially in those without degenerative complications, hypertension, and insulin therapy.

Outcome of Renal Transplant in Recipients With Vasculitis.

OBJECTIVES: End-stage renal disease develops in a high percentage of patients with vasculitis, in whom kidney transplant has become a therapeutic option. However, limited data are available on the prognosis and outcomes after kidney transplant in these patients. We aimed to compare the long-term graft survival and graft function in 8 renal transplant recipients with vasculitis (granulomatosis with polyangiitis, microscopic polyangiitis, Goodpasture syndrome, and Henoch-Schonlein purpura) with the other kidney recipients at a single center. MATERIALS AND METHODS: We conducted a retrospective study of patients followed for chronic renal failure associated with vasculitis before renal transplant. We excluded patients with no biopsy-proven nephropathy. RESULTS: There was no difference in the occurrence of metabolic and cardiovascular complications in our case group compared with the other graft recipients. Infections were frequent and included cytomegalovirus and urinary tract infection. The rates of bacterial and viral infection were equivalent in our population. The incidence of allograft loss was estimated at 1.8%, less than that seen in our entire transplant population. The presence of vasculitis was not significantly related to renal failure (P = .07). Extrarenal relapse occurred in 1 patient with microscopic polyangiitis. Antineutrophil cytoplasmic antibody levels in patients with granulomatosis with polyangiitis and microscopic polyangiitis did not seem to influence the renal outcome (P = .08). Circulating antineutrophil cytoplasmic antibodies were associated with the development of vascular lesions in the graft but were not significantly correlated with graft survival (P = .07). CONCLUSIONS: This study supports the theory that renal transplant is an effective treatment option for patients with end-stage renal disease secondary to vasculitis. These patients fare similarly to, if not better than, other patients.

[Membranoproliferative glomerulonephritis in patients with cryoglobulinemia complicating hepatitis C virus: report of 11 cases]. / Glomérulonéphrite membranoproliférative secondaire à une cryoglobulinémie mixte compliquant une hépatite virale C: a propos de 11 cas.

BACKGROUND: Membranoproliferative glomerulonephritis in patients with cryoglobulinemia complicating hepatitis C virus have yet been reported. Although, it remains controversial, antiviral treatment seems to be able to improve the outcome of glomerulonephritis. AIM: The objectives of the study were to analyze characteristics of this association and to report literature data and newness treatment. METHODS: It's a retrospective study including 11 patients with membranoproliferative glomerulonephritis, hepatitis C virus and mixed cryoglobulinemia. Hepatitis C virus antibodies was identified by ELISA technique. Hepatitis C virus genotype was identified in one patient. Cryoglobulins were isolated from sera of all patients at 37 degrees Celsius. RESULTS: Patients were 3 men and 8 women with a mean age of 51.9 +/- 15.5 years. Between the 11 patients, 7 had hypertension, 9 had nephrotic syndrome and 10 had chronic renal failure. Renal biopsy showed membranoproliferative glomerulonephritis lesions in all cases with fibrinoid thrombi in 8 cases. Six patients had chronic liver disease. Liver biopsy was performed in 4 patients, showing histological feature compatible with chronic active hepatitis in 2 cases. No patient had antiviral therapy. Renal failure was stable in 5 cases and progressed in 6 cases with end stage renal failure in 3 of them. One patient died, 4 months after diagnosis, because of severe pulmonary involvement in cryoglobulinemic vasculitis. In literature, treatment is dominated by antiviral therapy composed first by Interferon Alpha alone. Combination therapy associating Interferon and Ribavirin was recently used in renal involvement; it is clearly more effective than interferon alpha alone. CONCLUSION: Hepatitis C virus detection should be performed when membranoproliferative glomerulonephritis is associated with cryoglobulinemia. Antiviral treatment should be more widely used in Tunisia to evaluate his effect on renal involvement