Multiple Myeloma in a Young Adult with Renal Involvement.

Multiple myeloma (MM) results from malignant plasma cell disorder. It represents approximately 10% of hematological malignancies and it is typically diagnosed in the elderly with a median age of 70 years and has a steep increase in incidence with advancing age. N Engl J Med. 2004, 1860; Clin Interv Aging. 2020, 619. The incidence of MM has been increasing over time, mostly due to population aging. Mayo Clin Proc. 2010, 225 However, certain MMs are diagnosed at young age even under 40 years old (2%). Leuk Lymphoma. 1998, 493; Blood. 2010, 5501. We report a case of a MM in a thirty-four-year-old woman whose circumstance of discovery was acute kidney failure.

Thrombotic microangiopathy due to acquired complement factor I deficiency in a male receiving interferon-beta treatment for multiple sclerosis.

AIMS: Interferon-beta (IFNß), the most widely prescribed medication for multiple sclerosis, is generally considered safe. Nevertheless, rare serious and/or life-threatening side effects have been reported such as thrombotic microangiopathy. A few mechanisms have been proposed to explain how interferon causes thrombotic microangiopathy, but immunological studies have been unable to pin this phenomenon down to a single pathophysiologic pathway. The aim of this article was to report a new mechanism explaining Interferon beta related thrombotic microangiopathy. METHODS: We report thrombotic microangiopathy in a 28-year-old male receiving interferon-beta treatment for multiple sclerosis. RESULTS: After three years of starting interferon beta therapy, the patient presented with malignant hypertension causing seizures, rapidly progressive renal failure requiring haemodialysis and haemolytic anaemia. Corticosteroid and plasma exchange sessions permitted haemolysis control. Nonetheless, the patient remained hemodialysis-dependent. Exploration of the complement system found a complement factor I deficiency whose activity normalized at the control carried out after 2 years. CONCLUSION: IFNß treatment may cause complement factor I deficit, which can lead to thrombotic microangiopathy and severe renal failure.

Thirty years of experience with anti-neutrophil cytoplasmic antibody glomerulonephritis in Charles Nicolle Hospital-Tunisia: a retrospective cohort study.

Introduction: antineutrophil cytoplasmic antibodies (ANCA) associated Glomerulonephritis (GN) is rare but a life-threatening disease especially, particularly in patients with advanced renal failure at presentation. This study aims to evaluate the epidemiological, clinical and histopathological features of renal involvement and investigate factors associated with ESRD. Methods: patients with renal biopsy-proven ANCA associated glomerulonephritis were included retrospectively over a thirty years period. The renal survival, defined as time to reach ESRD, was evaluated based on clinical parameters, histopathological classification as well as the renal risk score. Results: a total of 65 patients with crescentic GN were included in the study. The mean age was 47.9 years ± 22.4 years (range: 18-78) with an M/F sex ratio at 1.13. Hematuria, proteinuria and oliguria were found in respectively 100%, 81.5% and 56.2% of cases. Sixty patients (92.3%) had renal failure at presentation, and 30 patients (46%) required initial hemodialysis (HD) therapy. The pattern of glomerular injury was categorized as mixed in 43.7% of cases, sclerotic in 34.3%, crescentic in 16.6%, and focal class in 6%. Regarding renal risk score, patients were classified in the category low risk, intermediate risk and high risk with respectively 16.9%, 44.6% and 38.4%. All patients received corticosteroids and immunosuppressive treatment. Complete, partial remission and relapses were noted in respectively 15.3%, 18% and 72% of cases. Factors associated with ESRD were serum creatinine level >500 µmol/l (P=0,0016), CRP level >60 mg/l (P = 0,0013), interstitial fibrosis (P=0,0009) and glomerulosclerosis> 10% of total glomeruli (P=0,001). The survival rate was 89%, 60.9% and 32.8% at respectively 1, 5 and 10 years. Death occurred in 10 cases (15%) caused mostly by infections (40%). Initial serum creatinine level>140 µmol/l (P=0,02), alveolar hemorrhage (P=0.001) and infections (P=0,0001) were associated with mortality. Conclusion: in our cohort of ANCA GN, confirms the data showing improved patient survival but constantly high relapse risk. In addition, we observed that ANCA GN classification was predictive, as the risk of progressing to ESRD increased with the ascending category of focal, crescentic, mixed and sclerotic GN.

Renal Amyloidosis: Epidemiological, Clinical, and Laboratory Profile in Adults from One Nephrology Center.

Background: Renal amyloidosis is one of the main differential diagnoses of nephrotic proteinuria in adults and the elderly. The aim of this study with the most important series in our country is to contribute to the epidemiological, clinical, and etiological study of the renal amyloidosis. Methods: In a retrospective study carried out between 1975 and 2019, 310 cases of histologically proven and typed renal amyloidosis were selected for this study. Results: There were 209 men and 101 women with a mean age of 53.8 ± 15.4 years (range, 17-84 years). Of the 310 cases, 255 (82.3%) were diagnosed with AA renal amyloidosis and 55 (17.7%) with non-AA amyloidosis. Infections were the main cause of AA amyloidosis, and tuberculosis was the most frequent etiology. The period from the onset of the underlying disease to diagnosis of the renal amyloidosis was an average of 177 months. The most frequent manifestations at the time of diagnosis were nephrotic syndrome (84%), chronic renal failure (30.3%), and end-stage renal disease (37.8%). After a medium follow-up of 16 months (range, 0-68 months), mortality occurred in 60 cases. Conclusions: Given the high frequency of AA amyloidosis in our country, awareness of the proper management of infectious and chronic inflammatory diseases remains a priority in reducing the occurrence of this serious disease.

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 and mantle cell lymphoma: a rare association.

Renal involvement in mantle cell lymphoma (MCL) is rare. We present the case of a man followed for MCL presented with acute kidney injury and positive antineutrophil cytoplasmic antibody (ANCA) type anti proteinase 3 (PR3). He was treated as for a rapidly progressing glomerulonephritis with cyclophosphamide and methylprednisolone followed by oral prednisone. Renal biopsy revealed diffuse endocapillary proliferation and segmental extracapillary proliferation in four glomeruli. Immunohistochemistry confirmed the renal invasion of lymphomatous cells. He started improving his renal function shortly after starting treatment. The coexistence of renal MCL infiltration, extracapillary proliferation and ANCA positive is exceptional.

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.

[Etiologies and prognostic factors of acute interstitial nephritis]. / Étiologies et facteurs pronostiques des néphropathies interstitielles aiguës.

INTRODUCTION: Acute interstitial nephritis represents a clinically and etiologically heterogeneous group of kidney diseases. The aim of our study was to explore the main causes of biopsy-proven acute interstitial nephritis and to identify predictive factors of renal outcome. METHODS: We conducted a retrospective monocentric study which included patients with biopsy proven AIN, followed in our department during the period between 1980 and 2018. The non-recovery of kidney function or an estimated glomerular filtration rate˂60 mL/min/1.73 m2 were considered as a worse renal outcome. RESULTS: A total of 65 acute interstitial nephritis patients were enrolled. The mean age of patients was 41.3±16 years with a female predominance (78%). Drug-induced etiology was the most common (29%). The most frequent culprit drugs in our study were NSAID followed by antibiotics. The renal prognosis was unfavorable in 21 cases (32%). The independent predictive factors for renal outcome were : a percentage of sclerotic glomeruli greater than 15% (P=0.004), absence of interstitial edema (P˂0.001), non-use to corticosteroid therapy (P=0.02) and a delay in initiating corticosteroid therapy greater than 21 days (P=0.02). CONCLUSION: Drugs currently represent the most common cause of acute interstitial nephritis. The renal prognosis is often favorable, but the progression can be towards chronic renal failure in the event of diagnostic and therapeutic delay. Our data suggest a beneficial influence of steroids on the outcome of acute interstitial nephritis.

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.

Multidisciplinary exams in medical studies : Interest of docimologic analysis.

Docimology has allowed the development of evaluative processes assuring valid, reliable and objective assessments. It was adopted within the faculty of Medicine of Tunis since  2007. The aim of this study was to analyze the docimological survey results of hematology-oncology exams, to evaluate the interest of this analysis in the elaboration of exams and the construction of an item bank, and propose some corrections  in order to improve assessment.     Methods :We have analyzed the hematology-oncology exams of SCMS1 (Second cycle of Medical Studies 1) from educational year 2008-2009 to 2013-2014. The data input was already done with Excel. The test includes 4 disciplines (Hematology, Oncology, Genetics and the Anatomic Pathology). We have calculated docimological parameters allowing global analysis, by discipline and by item. Results : A total of 3281 papers and 1004 questions were analyzed. The average success rate per year was 91,54% ± 7,12. The highest average success rate was found in hematology (80,51% ± 10,18). The lowest rate was found in the anatomic pathology (51,61% ± 23,76). The average rate of students succeeding the test without having average note in hematology was 5,36%. It was 42,29% in the anatomic pathology. Average difficulty index was 0,57 ± 0,05. Items analysis showed that 38,04% were easy and 19,02% were difficult. Average discrimination index was 0,25 ± 0,02. Discrimination was very good in 20,51% of items and good in 17,13%. Useless and bad discrimination items were about 40,53%. The average of Cronbach Alpha coefficient was 0,84 ± 0,03, showing a good internal-consistency. Conclusion :This study allowed an objective evaluation of "contributive disciplines" in multidisciplinary evaluation and showed the interest of integrating questions. Question analysis with teachers would be important to reevaluate and improve these items.

Clinical study on autosomal dominant polycystic kidney disease among North Tunisians.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, which usually manifests in adulthood. It is characterized by the development of multiple cysts in the kidneys and many other extrarenal manifestations. We aimed to determine the factors that contribute to the progression of ADPKD to end-stage renal disease (ESRD). In a retrospective multicentric study, we reviewed the records of 569 patients with ADPKD, hospitalized at a nephrology department or followed up at the outpatient department of university and regional hospitals, covering the north and center of the country, during the period 1969-2016. The mean age of the study patients was 48.54 ± 13.68 years and 14% were young adults (<40 years). There were 272 female and 297 male patients (sex ratio: male/female = 1.09). A family history of ADPKD was found in 43.7% of cases. Renal symptoms were dominated by loin pain, renal failure, hypertension, and hematuria, seen in, respectively, 51.9%, 48.2%, 29.1%, and 24.6% of the patients. The median serum creatinine level was 459 µmol/L (range: 47-2454), and hypertension had preceded the onset of ADPKD in 28.8% of cases. Extrarenal manifestations consisted of urologic complications (54.6%), liver cysts (43.5%), cardiac involvement (31.9%), cerebral aneurysms (12.9%), and gastrointestinal involvement (9.4%). ESRD occurred in 43.1% after a mean follow-up of 47 months (range: 0-384). Risk factors for poor renal prognosis were age >40 years (P = 0.009), hematuria (P = 0.034), hemoglobin >14 g/dL (P = 0.0013), high uric acid level (P = 0.001), and leukocyturia (P = 0.02). Death occurred in 59 cases (10.3%), mostly caused by infections (44.1%). In our study, ADPKD was lately diagnosed in most cases. Family screening is important, which will enable early detection and management of the complications associated with ADPKD.

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.

Urinary mRNA analysis of biomarkers to epithelial mesenchymal transition of renal allograft.

Renal allograft loss is most often a chronic process, irrespective of the mechanism at stake. In this prospective study, we studied the expression of epithelial to mesenchymal transition (EMT) markers vimentin and ß-catenin by immunohistochemistry in the surveillance biopsy and measured the mRNA encoding vimentin (VIM), CD45, GAPDH and uroplakin 1a (UPK) by quantitative PCR in urinary cells in 75 renal transplant patients. The aim is to establish a simple screening test for chronic renal allograft dysfunction. We found that the value of the mRNA of vimentin and CD45 relative to the uroplakin 1a (UPK) mRNA is correlated with the score in vimentin immunostaining in routine biopsies. These biomarkers could be used as a noninvasive tool to monitor the renal graft fibrogenesis. This test could be used for early detection of fibrotic diseases of the kidney transplant.