[Inherited kidney stones: A nephrology center experience]. / Lithiase urinaire héréditaire : expérience d'un service de néphrologie.

INTRODUCTION: Genetic factors must be considered in etiological diagnosis of urinary lithiasis. The aim of this study was to determine clinical, metabolic characteristics and the progression of hereditary urinary lithiasis in our patients. METHODS: A retrospective study was conducted between 2008 and 2018 and 60 patients were included. Patients were referred to our department from pediatrics departments to be followed-up in adulthood in 9 cases, for etiological investigation in 42 cases and for chronic renal failure in 9 cases. RESULTS: Thirty-five men and twenty-five women were enrolled in this study with a M/F sex ratio equal to 1.4. The mean age at the time of diagnosis of the hereditary character of the urinary lithiasis was 28.6years (3months-63years). The average delay between the onset of the lithiasis disease and the etiological diagnosis was 8years (0-42years). We noted 31 cases of cystinuria, 18 cases of primary hyperoxaluria type 1 with two mutations (I244T in 14 cases, 33-34 Insc in 23 cases) and 11 cases of renal tubulopathy. Fourteen patients were affected with chronic renal failure, of which five were in the end-stage renal disease. Crystalluria was positive in 62% of cases. The morpho-constitutional analysis of stones was performed in 37 cases and it contributed to the diagnosis in 29 cases. After an average follow-up of 16years, we noted normal renal function in 42 cases, chronic renal failure in 7 cases, hemodialysis in 10 cases all with primary hyperoxaluria and transplantation in 1 case. CONCLUSION: The etiological diagnosis of hereditary urinary lithiasis in our study was made with considerable delay. Cystinuria was the most frequent etiology and primary hyperoxaluria was the most serious affection. LEVEL OF EVIDENCE: 4.

Impact of Interleukin-17F Gene Polymorphisms in Outcome of Kidney Transplantation in Tunisian Recipients.

BACKGROUND: Genetic polymorphisms of interleukin (IL)-17F, associated with functional and/or quantitative change in this glycoprotein, have been described as predisposing to various autoimmune diseases. The proinflammatory IL-17 has some roles in renal transplantation. In this context, the relationship between the most common IL-17F polymorphisms with acute renal allograft rejection susceptibility in Tunisian renal recipients has been investigated. METHODS: We examined 93 renal transplant recipients who were enrolled and classified as follows: GI, 48 transplant recipients who developed at least one episode of acute rejection; and GII, 45 controls, kidney recipients who also were followed for at least 1 year and had stable renal function. Single nucleotide polymorphisms (SNPs) of IL-17F gene, including -1507 C/T (rs18889570), 7384 A/G (rs2397084), 7469 C/T (rs11465553), and 7489 A/G (rs763780), were evaluated using direct sequencing. RESULTS: No statistically significant association of the IL-17F SNPs studied with the onset of acute rejection was observed. However, AA genotype on 7489A/G SNP showed anti-HLA antibodies less than other genotypes and a higher graft survival time (P = .017). CONCLUSION: The AA genotype on 7489A/G SNP of IL-17F and the A allele might be associated with a lower risk of acute rejection with better graft survival.

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.

Nephrolithiasis-induced end stage renal disease.

INTRODUCTION: Nephrolithiasis still remains a too frequent and underappreciated cause of end stage renal disease (ESRD). METHODS AND PATIENTS: Of the entire cohort of 7128 consecutive patients who started maintenance dialysis in our nephrology department between January 1992 and December 2006, a total of 45 patients (26 women, 19 men) had renal stone disease as the cause of ESRD. The type of nephrolithiasis was determined in 45 cases and etiology in 42. The treatment and evolution of stone disease and patient's survival were studied. RESULTS: The overall proportion of nephrolithiasis related ESRD was 0.63%. The mean age was 48.4 years. Infection stones (struvite) accounted for 40%, calcium stones, 26.67% (primary hyperparathyroidism:15.56%; familial hypercalciuria: 4.44%, unknown etiology: 6.66%), primary hyperoxaluria type 1, 17.78% and uric acid lithiasis in 15.56% of cases. The mean delay of the evolution of the stone renal disease to chronic renal failure was 85.8 months. The feminine gender, obesity and elevated alkaline phosphatases >128 IU/L were significantly correlated with fast evolution of ESRD. The median evolution to ESRD was 12 months. The normal body mass index (BMI), medical treatment of stone and primary hyperoxaluria type 1 were correlated with fast evolution to ESRD. All patients were treated by hemodialysis during a mean evolution of 60 months. Sixteen patients died. The patient's survival rate at 1, 3 and 5 years was 97.6, 92.8 and 69% respectively. Hypocalcemia, cardiopathy and normal calcium-phosphate product were significantly correlated with lower survival rate. CONCLUSION: Severe forms of nephrolithiasis remain an underestimated cause of ESRD. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and efficient treatment for conditions leading to ESRD.

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.

Kidney transplantation: Charles Nicolle Hospital experience.

The aim of our retrospective study was to analyze the short- and long-term follow-up of 298 renal transplantations performed between June 1986 and May 2005. All were first transplantations except 4 cases, with 54 from cadaveric and 244 from living donors. The recipients included 196 males and 102 females of overall mean age of 31.21 +/- 8.9 years (range, 16-61 years). A combination of prednisolone and azathioprine was presented for 212 patients or mycophenolate mofetil for 86 patients. Polyclonal or monoclonal antibodies were used as induction therapy in 183 cases. Cyclosporine was administered to 188 cases and tacrolimus only to 16. HLA matching was 0 mismatches (MM) in 65 cases; 1 or 2 MM in 113; 3 MM in 99; and > or =4 MM in 21. Acute tubular necrosis occurred in 45 cases. One hundred eighteen patients experienced at least 1 acute rejection episode: 102 cases (41.8%) among living and 16 (29.6%) among cadaveric kidneys donor (P = .0007). The actuarial patient and graft survival rates at 1, 5, 10, 15, and 20 years were 95.9%, 87.4%, 77.5%, 65.6%, and 60.8%, and 94.9%, 84.5%, 75.4%, 65.4%, and 53%, respectively. Sixty-three patients died and 72 patients returned to dialysis. Our results were comparable to experienced centers. However, the member of kidney transplantations does not match the increased number of patients on renal replacement therapy. It is advisable to promote obtaining organs from brain-dead donors.

Avascular osteonecrosis after renal transplantation.

Avascular osteonecrosis (AVN) is a serious osseous complication after renal transplantation. Its prevalence clearly decreased from 20% to 4% after introduction of cyclosporine and reduction of steroid doses. The aim of our study was to evaluate the frequency of AVN among kidney transplant recipients and to determine the risk factors by comparing them with a population without AVN. Among 326 kidney transplant recipients between June 1986 and December 2004, 15 patients developed AVN with mean age of 40.86 years, including 11 men and 4 women. Fifteen kidney transplant recipients without AVN were selected to be matched for age, gender, and date of transplantation (control group). Cases of symptomatic AVN were diagnosed by hip X-ray, radioisotope bone scan, or magnetic resonance imaging. AVN was diagnosed at a mean of 3.5 years after transplantation (range, 0.5-13 years). The main localization of AVN was the femoral head in 12 cases and the femoral condyle in 3 cases. We studied the following risk factors: the type of donor (cadaver or living donor), the duration on dialysis before transplantation, the cumulative steroid dose, the acute rejection rate, and the posttransplantation weight gain. Statistical analysis showed that the cumulative steroid dose and the acute rejection rate were higher among the AVN group than the control group (P=.04 and P=.058, respectively). The prevalence of AVN in our population is 4.6%, which is probably an underestimate since these were symptomatic cases. The reduction or early withdrawal of steroids remains the only efficient preventive treatment for AVN.

[Renal manifestations in tuberous sclerosis]. / Atteinte rénale au cours de la sclérose tubéreuse de Bourneville.

BACKGROUND: Tuberous sclerosis is a rare inherited disease which can involve several organs. Renal involvement is one of the most severe manifestations of the disease. We analysed in this study renal involvement of tuberous sclerosis. METHODS: We studied retrospectively nine cases of tuberous sclerosis with renal involvement diagnosed between 1994 and 2005. The diagnosis was based on the presence of typical extra-renal manifestations and familial history of tuberous sclerosis. RESULTS: There were eight females and one male. Their mean age was 40.8+/-16.4 years (range: 15-62). At first presentation, we noted hypertension in three cases, proteinuria in seven cases, hematuria in eight cases and renal failure in five cases (end stage renal failure in four cases). By ultrasonography, we found angiomyolipoma in one case, cysts in four cases and angiomyolipoma associated to cysts in four cases. Nephrectomy was performed in two patients, in one case for hydronephrosis secondary to urolithiasis and in the other for hemorrhagic complication. In the later, pathological examination revealed renal carcinoma. At last evaluation, two patients were lost to follow-up, one had normal serum creatinine, five were on renal replacement therapy and the latter died from sepsis following kidney removal. CONCLUSIONS: In our patients, renal disease was diagnosed late at chronic renal failure stage. Patients with end-stage renal failure require dialysis and renal transplantation, but we recommend binephrectomy after starting dialysis and before transplantation due to the risk of cancer and bleeding related to angiomyolipomas.

[Indications, complications and cost of internal jugular catheters in hemodialysed patients: study of 533 cases]. / Indications, complications et cout des catheters jugulaires internes chez les hemodialyses: etude de 533 cas.

INTRODUCTION: Central venous catheters for hemodialysis are very useful as blood accesses when arteriovenous fistulas (AVF) are not available. The aim of this study is to analyse the clinical impact of internal jugular catheters (IJC) in hemodialysed patients and to assess their economic consequences. PATIENTS AND METHODS: It is a prospective study realised from July 1998 to March 2002 including 533 hemodialysed patients without functional AVF: 280 males and 253 females aged between 17 and 87 years (mean age: 54.1 +/- 15 years). Single lumen polyurethane Vygon were used. All catheters were placed using Seldinger procedure and the posterior route of Jernigan which is more comfortable for patient. RESULTS: Indications of IJC placement were new hemodialysed patients without AVF in 73.5% cases and no functional AVF in 26.5% cases. During the period of the study. IJC was placed in 533 patients. We failed to place the IJC at the first attempt in 42 patients but we succeed in placing it on the controlateral side. During IJC placement, we observed 50 (9.4%) cases of accidental puncture of carotid artery. The median duration use of IJC was 41 days (extreme: 1 to 413 days). IJC were removed mainly because of the use of AVF in 469 (88%) cases and the catheter infection in 41 (77%) cases. Bacteriological analysis were made only for 25 patients: staphylococci were identified in 16 cases and catheter cultures were negative in the 9 other cases. All patients were treated with antibiotics. Outcome was favourable for 39 of them and we had 2 deaths by septicemia. The IJC cost was 44,287 Tunisian Dinars (DT) coresponding to 31.633 Euro including 10125 DT (7,232 Euro) for infectious treatment. CONCLUSION: The use of IJC is frequent in our center with a high rate of infectious complications which increased the hemodialysis cost. The realisation of AVF, in patients with chronic renal failure before the beginning of hemodialysis, is the best way to limit the use of catheters.

[Lupus nephritis: 211 cases]. / Néphropathie lupique : à propos de 211 cas.

PURPOSE: Renal involvement is one of the most severe and frequent manifestations of systemic lupus erythematosus. Prognosis factors are variable in the different studies. We analyze in 211 patients clinical, biological and histologic characteristics of lupus nephritis and the different prognosis factors. METHODS: It's a retrospective study in 211 with lupus nephritis followed-up between 1975 and 2003. RESULTS: There were 195 women and 16 men aged meanly of 28,8 years. At first presentation, we noted hypertension in 32,3% of cases, nephrotic syndrome in 47,7% of cases and renal failure in 51,6% of cases. histologic examination of kidney revealed class III in 59 cases, class IV in 97 cases and class V in 33 cases. Two hundred and five patients were treated by corticosteriods associated with immunosupressive agents in 95 cases. After a mean follow-up of 103 months (2-289 months), we obtained remission in 55,3% deterioration of renal function in 34,8% with end stage renal failure in 14,7% and relapses occurred in 51% of cases. Thirty-three patients died. Age <24 years, hypertension, nephrotic syndrome and initial renal failure were statistically associated with deterioration of renal function. CONCLUSION: Lupus nephritis is severe in our patients with predominance of proliferative forms. Age <24 years, hypertension, nephrotic syndrome and initial renal failure were statistically associated with deterioration of renal function.

Renal amyloidosis followed more than 5 years: report of 12 cases.

Renal involvement with amyloidosis is common but causes patient survival to be poor, rarely reaching 5 years. In this study, we retrospectively reviewed clinical and biological characteristics as well as treatments and outcomes of patients with renal amyloidosis followed for more than 5 years. Between 1975 and 2003, 485 patients were diagnosed with renal amyloidosis including only 12 patients who were followed more than 5 years. The six men and six women of mean age 42.4 years (range 18 to 66 years) displayed renal signs of lower limb edema in all cases; hypertension in four cases, proteinuria on urinalysis in all cases with microscopic hematuria in five cases. Biological tests showed nephrotic syndrome in 11 patients, normal renal function in nine patients, and renal failure in three patients whose mean creatinine was 481.6 micromol/L (range 294 to 726). The amyloidosis was AA type in 11 cases and non-AA in one case. An etiologic survey revealed spondylarthropathy in one patient, pulmonary tuberculosis in two patients, chronic bronchitis in three patients, hepatic hydatic cyst in one patient, Mediterranean familial fever in two patients, Crohn's disease in one patient, Hodgkin's lymphoma in one patient, and multiple myeloma in one patient. Specific treatment was initiated with colchicine in seven patients. At a 110-month mean follow-up (range 53 to 153 months), remission of nephrotic syndrome was observed in four cases, progression to chronic renal failure in two patients, and to end-stage renal failure in five cases (range 53 to 196 months), with stabilization of renal function in seven patients. In conclusion, primary amyloid disease should be optimally suppressed in patients with renal involvement. The role of this treatment in remission of renal amyloidosis is not well established. This efficacy of the treatment has been demonstrated in some patients with improved survival.

Impact of initial blood pressure on the mortality of diabetics undergoing renal replacement therapy.

The aim of this study was to determine the blood pressure (BP) profiles and their impact on mortality among a cohort of uremic diabetics treated by hemodialysis. The studied population includes all type II diabetics starting hemodialysis for end-stage renal disease between 1990 and 1996. There were 221 patients (144 men, 77 women) aged from 37 to 78 years, were all followed until death or December 2003 without any censored data. Survival analysis to identify predictors of death was performed using the actuarial method, Cox proportional model, including systolic, diastolic, mean, and pulse blood pressures (SBP, DBP, MBP, PP). One hundred seventy-eight patients (80.5%) were hypertensive at the start of dialysis. Hypertension preceded the diagnosis of diabetes in eight cases (4.5%); 154 patients (86.5%) received antihypertensive drugs and only 23 (14.9%) had well-controlled hypertension. Our population was subdivided into four groups according to their BP levels at the time of beginning of dialysis; G1 (19.5%): normal BP (SBP [90 to 140] and DBP [60 to 90]); G2 (30.3%): Hypertension stage 1 (SBP [140 to 160] and/or DBP [90 to 100]); G3 (32.1%): hypertension stage 2 (SBP [160 to 180] and/or DBP [100 to 110]); G4 (18.1%) hypertension stage 3 (SBP [180 to 220] and/or DBP [110 to 120]). Mean age and comorbidities were similar among the four groups. During a cumulative follow-up period of 872 patient-years, 191 patients died, representing a rate of 21.9 per 100 patient-years; 20.42% of these deaths occurred during the first 3 months of dialysis. Normotensive patients showed lower survival rates without any significant difference in comparison with those of other hypertensive groups. None of the initial BP parameters (SBP, DBP, PP, MBP, hypertension stages) seemed to influence early or global mortalities, which were rather related to the urgent onset of renal replacement therapy, to age, to serum albumin, and to the score of associated morbidities. We conclude that mortality of our hemodialyzed diabetics was not influenced by the blood pressure parameters recorded at the onset of dialysis.

[Sternal metastasis revealing hepatocarcinoma]. / Métastase sternale révélatrice d'un hépatocarcinome.

INTRODUCTION: Bone metastasis from hepatocarcinoma are rare, their elective seats are the ribs, the vertebra and rarely the sternum. We report a case of a sternal metastasis which makes discovery of a hepatocarcinoma. EXEGESIS: A 64 year-old man, alcoholic with a previous history of jaundice who developed since 1999 an anterior chest tumor with excellent clinical condition. Laboratory examination showed cytolysis, cholestasis, positive antihepatitis C virus antibodies and elevated serum alphafetoprotein level. Standard radiography and computed tomography of the chest showed an osteolytic lesion of the sternum spread to the adjacent soft tissues and voluminous right hepatic lesion. Pathologic examination of the sternal tumor concluded to a differential adenocarcinoma. Etiologic investigations to find the primitive tumor were negative. Operative procedure was not possible in consideration of the infiltration of the tumor and its situation near the main blood vessels. Radiotherapy gives rise to partial regression of the tumor. A second reading of the tumor biopsy established the diagnosis of metastasis from a hepatocellular carcinoma. The patient died 22 months after the appearance of the sternal metastasis. CONCLUSION: Hepatocarcinoma is rarely disclosed by a sternal metastasis, our case-report is particular by its prolonged survival and the good clinical condition during its follow up.

Autoantibodies to ribosomal P proteins in systemic lupus erythematosus.

UNLABELLED: Autoantibodies to ribosomal P proteins (anti-P) are directed against three ribosomal phosphoproteins (P0, P1, and P2) and are believed to be specific markers for systemic lupus erythematosus (SLE), particularly with neuropsychiatric manifestations. The objective of this study was to determine the rate of occurrence and clinical significance of anti-P in Tunisian patients. METHODS: We included 100 Tunisian patients with SLE whose sera were received between January 1998 and December 2000 by the immunology laboratory of the Charles Nicolle Teaching Hospital in Tunis, Tunisia, and were tested for anti-P. An immunodot technique based on a synthetic protein shared by all ribosomal phosphoproteins was used. RESULTS: Sera from 22 (22%) patients were positive for anti-P. This rate is consistent with the literature. We found no statistically significant associations between anti-P and specific manifestations of SLE. CONCLUSION. We found that anti-P were significantly associated with anti-Sm and anti-RNP, as reported previously. The significance of these associations remains debatable.

Renal replacement therapy for diabetic end-stage renal disease. Experience of a Tunisian hospital centre.

OBJECTIVE: To determine the epidemiological and clinical characteristics of 299 uremic diabetics at the initiation of renal replacement therapy (RRT) and to evaluate their morbidity and the factors influencing their mortality during the dialysis period. PATIENTS AND METHODS: All patients starting RRT for diabetic end-stage renal disease (ESRD) at Charles Nicolle Hospital of Tunis during a period of seven years (1990-1996) constituted the study population. During the follow-up period ended on December 31, 2000, all morbid events, hospitalizations and deaths were recorded. Multivariate analysis according to the Cox proportional hazards model was performed to identify the predictors of mortality. RESULTS: There were 238 type 2 (79.6%) and 61 type 1 diabetics (20.4%) representing 20.3% of all patients accepted for RRT. The mean age at the onset of RRT was 53.16 +/- 12.43 years (range: 23 to 80 years). A poor glycemic control was observed in 46.7% of type 2 diabetics and in 67.3% of type 1 diabetics (p=0.0055). A third of patients started RRT in emergency conditions and 91% required a temporary vascular access. At the time of onset of RRT, 86.7% of patients were hypertensive and 52.1% had a nephrotic syndrome. Blindness was observed in 22.9% of type 1 diabetics and in 7.5% of type 2 diabetics (p=0.0014). During the follow-up period, 217 patients died representing a rate of 22% patient-years, 26.7% of these deaths occurred during the first 3 months of RRT and 53% were attributed to infectious or cardiovascular complications. Actuarial survival rates were 68.4%, 59.6% and 45.3% at 1, 2 and 4 years, respectively. Age, co-morbidities and conditions of onset of RRT were independently correlated with survival time. CONCLUSION: Diabetes is a frequent cause of ESRD in Tunisia, the delayed referral to a nephrologist and coexistence of serious co-morbidities at the initiation of RRT resulted in a high rate of early death. Greater efforts should be made in our country in view of improving the quality of medical care of uremic diabetics before and during RRT.

Influence of surgery on renal amyloidosis.

It is well known that renal amyloidosis (RA) leads to ESRD in a few years. This evolution may be accelerated by several factors such as steroids, renal vein thrombosis, infections or surgery. We report 22 patients (14M,8F) mean age = 41.6 years (13-72) with RA in whom surgery revealed or aggravated renal disease. The group I includes 15 patients with no previous history of renal disease and who developed oedema few days after surgery with acute renal failure in 5 of them. Proteinuria was present in all the cases with a nephrotic syndrome in 10. Percutaneous kidney biopsy (KB) showed renal amyloidosis in all patients (AA+ = 8 cases, AA- = 3 cases). Only 9 patients were followed-up (mean period = 40 months): 2 patients are stationary; 1 is on complete remission 2 are on HD and 4 died. The group II includes 7 patients with a previous history of nephropathy (Histologically proven amyloidosis: 3 CRF = 1, Oedema: 3). All these patients developed oedema few days after surgery with acute RF in 4 patients. KB performed in all of them showed RA (AA+ = 33, AA- = 1). 6 patients were followed up for a mean period of 11 months: 5 died, 1 patient is on HD. The influence of surgery on renal amyloidosis is often unforeseeable. It may have no effect on renal disease, but very often it reveals RA and sometimes dramatically aggravates the course of the disease with occurrence of irreversible CRF. The pathogenic role of surgery on RA is discussed.