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.

End-stage renal disease at dialysis initiation: Epidemiology and mortality risks during the first year of hemodialysis.

Chronic kidney disease (CKD) treated by hemodialysis (HD) is a worldwide major public health problem. Its incidence is getting higher and higher, leading to an alarming social and economic impact. The survival of these patients is significantly low, especially during the first year of treatment. The purpose of our study was to identify the epidemiological and clinico-biological characteristics of patients at the HD initiation and to reveal the predictive factors of mortality at three months and one year of HD. This is a prospective, analytical, and descriptive study dealing with 229 patients with an end-stage renal disease (ESRD), followed up in the Nephrology Department of Charles Nicolle Hospital and La Rabta Hospital in Tunisia, that was started HD between January and June 2017. A multivariate logistic regression analysis allowed us to identify the independent predictors of mortality at three months and one year. The average age was 60.2 ± 15.3 years, with a gender ratio of 1.41. Seventy-eight percent of patients had more than two comorbidities, 59% had diabetes, and 88% had hypertension. Diabetic nephropathy was the leading etiology of kidney disease (48.9%), while 11% of nephropathies were of unknown etiology. Only 58% were early referred to a nephrologist. The average glomerular filtration rate at HD initiation was 6.06 ± 2.33 mL/min/1.73 m2. Hypocalcemia and hyperphosphatemia were noted, respectively, in 60.8% and 84.9% of cases. Anemia was objectified in 98.6% of cases. HD was started in an emergency in 56.8% of cases. One of the most urgent indications was acute pulmonary edema (APE) for 43.8% of patients. Only 10.5% of patients had functional arteriovenous fistula at the dialysis initiation. Patients were hemodialyzed one, two, or three sessions per week, respectively, in 23.2%, 26.6%, and 50.2% of cases. The crude mortality rate was 25% and 13% in, respectively, one year and three months of HD. On multivariate analysis, we identified heart failure and insufficient dialysis dose per week as predictive factors of mortality at the 1st year of HD. C-reactive protein more than 21 mg/L, insufficient dialysis per week, modified Charlson Comorbidity Index less than 6, and APE at the dialysis initiation were identified as predictive factors of three-month mortality. Despite the short period of study, this work revealed the alarming conditions of patients at HD initiation. This critical situation is due to the delay in CKD diagnosis, the late nephrologist referral, and the lack of preparation before HD initiation.

PLA2R antibody, PLA2R rs4664308 polymorphism and PLA2R mRNA levels in Tunisian patients with primary membranous nephritis.

BACKGROUND: Primary membranous nephritis (PMN) is an autoimmune disease induced by the deposit of antibodies (Ab) to the phospholipase receptor A2 receptor (PLA2R) on podocytes. In this context, we aimed to assess the relationships between anti-PLA2R Ab, PLA2R rs4664308 SNP, PLA2R mRNA levels and PMN susceptibility and outcome. METHODS: Sixty-eight PMN patients, 30 systemic lupus erythematosus (SLE) patients with secondary MN and 30 healthy control subjects served for anti-PLA2R Ab measurement by ELISA and PLA2R rs4664308 SNP genotyping by a commercial real-time PCR. Twenty patients with tubulo-interstitial nephritis (TIN) were used as controls for renal PLA2R mRNA quantification in PMN patients from kidney biopsies. PLA2R mRNA quantification was carried-out by real-time PCR after RNA extraction. RESULTS: Forty-three (63.2%) PMN patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant PMN to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) PMN patients, while all SLE patients and controls were negative, p<0.0001. Moreover, anti-PLA2R Ab levels were significantly higher in PMN patients (134.85 [41.25-256.97] RU/ml) than in SLE patients (3.35 [2.3-4.35] RU/ml) and controls (2 [2-2.3]), p<0.0001. Consequently, a ROC curve showed for 100% specificity a sensitivity of 94.1% at a threshold of 2.6 RU/ml. Besides, Anti-PLA2R antibodies levels were significantly associated to non-remission; p = 0.002. The rs4664308*A wild-type allele was significantly more frequent in PMN patients (0.809) than in controls (0.633) and SLE patients (0.65); p = 0.008, OR [95% CI] = 2.44 [1.24-4.82] and p = 0.016, OR [95% CI] = 2.27 [1.15-4.5], respectively. Renal PLA2R mRNA levels were significantly higher in PMN patients (218.29 [66.05-486.07]) than in TIN patients (22.09 [13.62-43.34]), p<0.0001. Moreover, PLA2R mRNA levels were significantly higher in non-remission patients (fold-factor vs. partial remission = 2.46 and fold-factor vs. complete remission = 12.25); p = 1.56 10E-8. In addition, PLA2R mRNA and anti-PLA2R Ab levels were significantly correlated, Spearman Rho = 0.958, p<0.0001. CONCLUSION: Anti-PLA2R Ab and renal PLA2R mRNA could be useful markers for PMN outcome predicting. The PLA2R rs6446308 SNP is associated with PMN susceptibility in Tunisians.