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.

The pattern of histologically-proven acute post-infectious glomerulonephritis in Tunisian adults seen in 1976-2004.

INTRODUCTION: Acute post-infectious glomerulonephritis (APIGN) is uncommon in adults. It is widely recognized that the prognosis of APIGN is good in children. There is however little information about its long-term prognosis in adults. METHODS: Between December 1976 and October 2004, 148 adult cases of APIGN were managed in our center. We retrospectively reviewed these patients' records and evaluated their clinical course and outcome. RESULTS: The mean age of studied patients was 36 ± 15 years, and the male to female ratio was 2.3. The most common site of preceding infection was the respiratory tract (68.8%). At presentation, 89.2% had nephritic syndrome and 9.4% had rapidly progressive glomerulonephritis. Proteinuria was observed in 99.3%, hematuria in 95.3%, peripheral edema in 89.2% and hypertension in 81.8%. Most patients (60.7%) had acute kidney injury and four patients (2.7%) required dialysis. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis in 88.8% of patients, associated with extracapillary proliferation in 12%. After a median follow-up of 2.5 year, only two patients died and 16.12% of patients had persistent clinical and/or biological abnormality. Chronic kidney disease was noted in 10 patients (6.75%) including four patients (2.7%) who progressed to end-stage renal disease. Poor prognostic factors included nephrotic range proteinuria, extracapillary proliferation in renal biopsy, acute kidney injury and the need for dialysis. CONCLUSION: In this cohort of patients, APIGN progressed to chronic kidney disease in less than 10% of patients.

Comparison of C-reactive protein and high-sensitivity C-reactive protein levels in patients on hemodialysis.

Chronic inflammation is highly prevalent in patients on hemodialysis (HD), as evidenced by increased levels of C-reactive protein (CRP). We compared CRP to high-sensitivity C-reactive protein (hs-CRP) to determine whether it has any clinical implications and prognostic significance in terms of mortality. CRP was measured using a standard immunoturbidometric assay on the COBAS® INTEGRA system and hs-CRP was measured using the Dade Behring on the Konelab Nephelometer in 50 patients on HD. CRP (≥6 mg/L) and hs-CRP (≥3 mg/L) levels were elevated in 30% and 54% of the patients, respectively. A significant correlation was noted between hs-CRP and CRP levels (r = 0.98, P <0.001). Deming regression analysis showed that the slope was near one (r = 0.90; 0.83-0.94) and that the intercept was small. Multivariate regression confirmed that age above 40 years (RR = 3.69, P = 0.027) and duration on HD greater than five years (RR = 3.71, P = 0.028) remained significant independent predictors of serum hs-CRP. Thirteen patients died during follow-up (26%). Multivariate Cox regression demonstrated that hs-CRP (RR = 1.062, P = 0.03) and CRP levels (RR = 1.057, P = 0.009) and age (RR = 1.078, P = 0.001) were the most powerful predictors of mortality. The CRP standard assay presents a reasonable alternative to the hs-CRP assay in patients on HD. The advantages of the CRP standard assay are its online and real-time availability as well as lower costs, particularly in developing countries.

International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4.

Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS.

Clinicopathological characteristics of obesity-associated focal segmental glomerulosclerosis.

Obesity-related glomerulopathy (ORG) is a secondary form of focal segmental glomerulosclerosis (FSGS) occurring in obese patients with a body-mass index higher than 30 kg/m(2). It is typically manifested by nephrotic-range proteinuria without full nephrotic syndrome, and progressive renal insufficiency. Characteristic morphologic features include the consistent presence of glomerulomegaly, predominance of perihilar variant of FSGS, and the relatively mild fusion of visceral epithelial cell foot processes. The concept of podocyte depletion as a driver of the glomerular scarring in obesity-associated FSGS is well documented. The underlying mechanisms are likely to be related in part to the oxidative stress and the impairment of the integrity of the slit diaphragm and cell adhesion resulting mainly from angiotensin II and transforming growth factor-ß. These proapoptotic cytokines are upregulated in obesity in response to insulin resistance, compensatory hyperinsulinemia and glomerular hyperfiltration-hypertension mediated mechanical stress. This review is designed to discuss the clinicopathologic features of obesity-associated FSGS, with a focus on the podocyte injury, which is involved in the onset and progression of the glomerulosclerotic process. Ultrastructural glomerular lesions are documented.

[Association of post-transplant lymphoproliferative disease and visceral leishmaniasis after kidney transplantation]. / Association d'un syndrome lymphoprolifératif et d'une leishmaniose viscérale après transplantation rénale.

Malignancies and opportunistic infections are frequently observed after solid-organ transplantation. Their occurrence strongly affects recipient survival. We report the case of a 29-year-old Tunisian kidney-recipient who was diagnosed simultaneously with post-transplant lymphoproliferative disease (PTLD) and visceral leishmaniasis (VL). Withdrawal of immunosuppressive therapy together with antiparasitic treatment using liposomal amphotericin B, and anti-CD20 antibodies medication resulted in cure of leishmaniasis and remission from PTLD. This case is of clinical interest because of the uncommon association of VL with PTLD after solid organ transplantation. It is also original by the favourable outcome of VL and PTLD, both known as life-threatening diseases. Also, it illustrates the predisposing role of immunosuppressive therapy in occurrence of opportunistic infections and malignancies after solid organ transplantation.

Membranoproliferative glomerulonephritis with isolated C3 deposits: case report and literature review.

Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.

[Renal involvement in Behcet's disease]. / L'Atteinte Renale au cours de la Maladie de Behçet.

BACKGROUND: Renal involvement in the Behcet's disease is rare. The clinical features vary from urinary sediment's abnormalities to ESRD. AIM: We propose to study the clinical, biological and histological data, the therapeutic management and the prognosis of patients. METHODS: We report a retrospective study including 8 patients representing 1.23 % of cases. RESULTS: The average age of the patient was of 37 +/- 12. 35 years with a clear male prevalence. Urinary signs were discovered fortuitously by the strips in the majority of the cases after an average of 18 months. It's about proteinuria and hematuria. Renal insufficiency and hypertension were rare. Pathological study highlighted 3 cases of amyloidosis, 2 cases of IgA nephropathy, 1 case of minimal change disease, 1 case of endo and extracapillary glomerulonephritis and 1 case of interstitial nephropathy. Patients having GN were treated by corticoids and immunosuppressive agents and those having an interstitial nephropathy were treated symptomatically with good evolution in the majority of the cases. Only one patient is dead, he had amyloidosis. Prognosis depended on the precocity of the diagnosis, the histological type and the treatment. CONCLUSION: The renal involvement during Behçet's disease is rare. Amyloidosis and Ig A nephropathy are the most frequent. Treatment is still controversial.

[Calciphylaxis in chronic renal failure: 3 cases]. / Calciphylaxie au cours de l'insuffisance rénale chronique: etude de 3 cas.

BACKGROUND: Calciphylaxis is a small vessel disease responsible for vascular calcification and skin necrosis. It occurs in association with chronic renal failure and has a poor prognosis. BUT: Report new cases. We report 3 cases of calciphylaxis occurred in patients with chronic renal failure secondary to interstitial nephritis in 1 case, diabetic nephropathy in 1 case and thrombotic microangiopathy in 1 case. CASES: They were 2 females an 1 man aged of 44, 3 years meanly. Hyperphosphoremia and hyperparathyroidism were the essential risk factors. All patients died by sepsis. This course was precipitating by corticotherapy in 2 cases. CONCLUSION: Early recognition and treatment of risk factors is mandatory to reduce mortality in uremic patients with calciphylaxis.

[A rare case of Graves' disease in a patient on regular haemodialysis]. / Un cas rare de maladie de Basedow chez un patient hémodialysé chronique.

INTRODUCTION AND AIMS: Abnormal thyroid hormone production and metabolism are relatively common in chronic renal failure and in regular haemodialysis. Graves' disease is a very unusual condition and is difficult to identify. We report a case of Graves' disease in a patient on regular hemodialysis. CASE REPORT: A 26-year-old man undergoing regular hemodialysis from unknown chronic nephropathy since four years. The patient suffered from unexplained slimming and aggressiveness. On admission, he had an irritability, tremor of the extremities, arterial hypertension not controlled by the medical treatment, discrete asynergy oculo-palpebral, glare of the glance and protrusion of the ocular spheres. The thyroid was non palpable. Biological tests demonstrated hyperthyroidism. Thyroid-stimulating hormone receptor antibodies were positive. Thyroid echography and scintiscanning showed vascular and hyperfonctionnel character of the thyroid. The patient was treated radically by radioactive iodine 131 therapy after medical preparation by antithyroid agent. He developed hypothyroidism treated by substitutive treatment. CONCLUSION: The diagnosis of Graves' disease must be evoked even in the absence of specific symptoms in haemodialysis patients. In front of clinical symptoms, since the conventional treatment is effective and inoffensive.

[Nephrology in Tunisia: From yesterday to now]. / La néphrologie en Tunisie : d'hier à aujourd'hui.

Professor Hassouna Ben Ayed is the founder of Tunisian nephrology. He introduced in 1962 the first artificial kidney for the treatment of acute renal failure. In 1963, the first acute peritoneal dialysis was done. Renal biopsy started in 1967 with general pathologists. A special laboratory of renal pathology was set up in 1975 with Pr H. Ben Maïz. Epidemiology of glomerular diseases, when histologically proven, was published [8]. A comprehensive program of chronic hemodialysis was started in 1968 and was developed markedly since 1975 with Pr A. El Matri. An intermittent peritoneal dialysis programme was started in 1982 and CAPD in 1983 by Pr T. Ben Abdallah. The Tunisian renal failure patient association was created in 1982 and the Tunisian society of nephrology in November 1983. A national registry for ESRD treatment is available since 1986. Since this time, the number of patients initiating renal replacement therapy (RRT) for ESRD has increased dramatically due to the extension of acceptance criteria for RRT and the increase of the elderly population. The incidence was 13 pmp in 1986 and 133 pmp in 2008. The prevalence was 48.5 pmp in 1986 and 734 pmp in 2008. From 1971 up to 1986, locally dialysed patients have been transplanted abroad, especially in France. On 4 June 1986, the local transplantation program was started at Charles Nicolle Hospital in Tunis. A national center of organ transplantation was created on 12 June 1995. At the end of 2008, there were 106 nephrologists, 26 residents in nephrology and 253 doctors with a training in hemodialysis during 1 year. In university hospitals, the number of nephrology departments is five, with one unit in an army hospital and two units for pediatric nephrology. Five hospitals perform renal transplantation (Tunis: 2 - Sfax: 1 - Sousse: 1 - Monastir: 1). There are 138 centers of hemodialysis: 39 public, 99 private. Seven thousand and eighty patients were treated by HD, 127 patients underwent renal transplantation. The vast majority of these transplants have been performed using living related donors (103/127). The cost of renal replacement therapy (RRT) is taken in charge by the Ministry of Health and the national security boards. Legislation on HD was promulgated by the Tunisian government, setting rigorous and detailed rules for the implementation of new dialysis centers, as well as for the functioning of already active units (4 August 1986 - 4 April 1998). For transplantation, legislation was promulgated on 25 March 1991.

[Colic angiodysplasia and chronic haemodialysis. Argon plasma treatment. A case report]. / Angiodysplasie colique et hémodialyse chronique. Traitement par coagulation au plasma argon. A propos d'un cas.

INTRODUCTION: Gastrointestinal angiodysplasia is a very common cause of digestive haemorrhage among patients with chronic renal insufficiency. It is well known that bleeding from angiodysplasias can be a difficult therapeutic problem since therapeutic possibilities are scarce and surgery is scolded with high mortality rate. Endoscopic argon plasma ablation therapy is a new, effective and safe treatment in the management of gastrointestinal angiodysplasia. CASE REPORT: We reported a case of a female haemodialysis patient aged 40 years. She was haemodialysed since 6 years in our center from unknown nephropathy. In March 2006, she complained of black stools and melena, and developed severe anaemia (Haemoglobin at 4 g/dL). Exploratory endoscope examination of the digestive tract showed the presence of bleeding from angiodysplastic lesions of the right colon. The patient had severe clinical picture extension of angiodysplastic lesions and frequent bleeding episodes. Bleeding arrest was observed after argon plasma coagulation, with a significant decrease of blood transfusions and improvement of anaemia. CONCLUSION: Gastrointestinal angiodysplasia was reported to be an important complication in dialysis patients and was recognized as an important cause of erythropoietin-resistant anaemia. It can worsen vital prognosis. Argon plasma coagulation is an effective treatment in these patients.

The G1057D polymorphism of IRS-2 gene is not associated with type 2 diabetes and obese patients among ethnic groups in Tunisian population.

BACKGROUND: Type 2 of diabetes is the most common metabolic disorder and results from the interaction between genetic and environmental factors. Insulin receptor substrate-2 (IRS-2), one of the major substrates of the insulin receptor, has a crucial role in insulin signalling and in beta cell development and survival. While several polymorphisms have been identified in the IRS-2 gene, the association of the Gly1057Asp polymorphism with type 2 diabetes has been studied in European and Chinese populations, but the results have been inconsistent. OBJECTIVES: The aim of this study was to investigate the association of Gly1057Asp polymorphism in insulin receptor substrate-2 (IRS-2) gene among patients with type 2 diabetes in well defined ethnic groups from Djerba Island in Southeastern Tunisia. METHODS: The studied population (172 Arabs and 100 Berbers) includes 162 patients with type 2 diabetes and 110 healthy controls. BMI was calculated for each subject. The subjects were unrelated and randomly selected Arabs and Berbers were equally distributed between controls and diabetics. The G1057D polymorphism of the IRS-2 gene was genotyped using PCR-RFLP assay. RESULTS: This case/control study indicated that frequency of the IRS-2 Gly1057Asp polymorphism was not significantly different between the healthy controls and type 2 diabetic groups, neither between healthy nor obese subjects, in both ethnic groups. Moreover, this polymorphism is present at a lower frequency in Djerbian than in neighbouring European populations. CONCLUSION: These results strongly argue against a major role of the Gly1057Asp IRS-2 polymorphism in the pathogenesis of type 2 diabetes in Djerbian subjects.

Association of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene with type 2 diabetes in two ethnic groups of Jerba Island in Tunisia.

INTRODUCTION: The aim of the current study was to evaluate the role of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on the prediction of type 2 diabetes in two ethnic populations from Jerba Island,Tunisia. METHODS: In this study, we analysed the genotypic and the allelic distributions of the ACE I/D polymorphism and conducted a case/control association study between healthy normoglycaemic controls and diabetic patients in the two studied groups.ACE gene polymorphism was analysed by polymerase chain reaction in 272 individuals consisting of 172 diabetic subjects and 100 controls. RESULTS: The genotype frequencies for DD, ID and II were 75.50%, 19.60% and 4.89% inArabs and 76.66%, 16.66% and 6.67% in Berbers, respectively, in the case group, and 42.85%, 35.71% and 21.43% inArabs and 57.50%, 22.50% and 20.00% in Berbers, respectively, in the control group.The DD frequency was significantly higher in the case group than in the control group (p<0.001), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study populations. CONCLUSIONS: The current investigation provides new evidence regarding the role of the ACE I/D polymorphism in the pathogenesis of type 2 diabetes in Jerbian populations. Furthermore, it underlines the importance of ethnicity, which should be considered in all studies aiming to test the genetic effects on the susceptibility to type 2 diabetes.

[Peritoneal dialysis in the elderly]. / La dialyse peritoneale chez le sujet age.

BACKGROUND: Peritoneal dialysis is used more and more as treatment of substitution of the end stage renal disease at the old subjects of more than 65 years and its effectiveness and its good tolerance were shown. AIMS: To study the epidemiological and clinical profile of these patients, the indication and the advantages of PD, the various complications, the elements of prognostic and the survival of the patients and the technique. METHODS: We made a retrospective study including a series of 13 old patients of more than 65 years and treaties by PD during the period extending from the 1983/2/11 to the 2005/12/31. They are 10 men and 3 women on average of 70 +/- 3.1 year and representing 3.62% of the totality of the patients. The diabetic and vascular nephropathies represent the first cause of ESRD. RESULTS: The PD was used of first intention at 53.84% of the patients whose majority suffers from a malnutrition due to advanced age, anorexia, psychological disorders, bad dental state and uraemia. The cardiovascular complications are frequent in this age bracket explaining heavy morbidity. The pulmonary and urinary infectious complications are also frequent. The more frequent peritonitis compared to the literature, are comparable between the 2 age brackets < and = with 65 years and the mode of PD (APD or CAPD). The time separating the beginning from PD and which has occurred of the peritonitis is shorter in APD. The lesions of renal osteodystrophy are found among 6 patients: 3 cases of hyperparathyroidism and 3 cases of adynamic osteopathy. The return in HD is rare due to dysfunction of the catheter. The survival of the patients is 92.8% at 1 year and 60.8% at 5 years; that of the technique is worse with 88.3% at 1 year and 33.7% at 5 years Eight patients died (61.5%) because of cardiovascular diseases and of the infections. We found a correlation statistically significant between the survival of the patients and the mode of PD, on the other hand any correlation was not found with the age or the sex. The survival of the technique is not correlated to a significant degree with the age, the sex and the mode of PD. CONCLUSION: Peritoneal dialysis is used of first intention at more half of the old subjects and remains a last recourse for haemodialysis which have an initially vascular problem. The family support and the good nurse allow these patients to adhere well to the technique. The cardiovascular diseases and the infections are responsible for heavy morbi-mortality. The survival of the technique is worse than that of the patients.

Influence of socioeconomic lifestyle factors and genetic polymorphism on type 2 diabetes occurrences among Tunisian Arab and Berber groups of Djerba Island.

Type 2 diabetes mellitus (T2DM) is characterized by three major metabolic abnormalities: impaired insulin-stimulated glucose uptake in muscle and adipose tissues, alterations in glucose-stimulated insulin secretion, and increased hepatic glucose production. Both genetic and environmental factors contribute to its development. The insulin gene (INS), insulin receptor gene (INSR), and insulin receptor substrate 1 gene (IRS1), identified by polymerase chain reaction and digestion with selected restriction enzymes PstI, NsiI, and BstnI, have been proposed as T2DM candidate genes. To determine the contribution of genetic and environmental factors on the occurrence of T2DM, we examined the frequency of T2DM among two ethnically diverse populations, Arabs and Berbers, who have shared the same environment, the island of Djerba, for thousands of years. Both populations have a high prevalence of obesity,T2DM, and a high consanguinity rate. A total of 162 T2DM men and women were matched to 110 healthy male and female controls. Results showed that the NsiI polymorphism in INSR and BstnI polymorphism of IRS1 were significantly associated with T2DM only among the Berber group. The PstI polymorphism in INS, was not associated with T2DM in either group. Sedentary lifestyles, lower physical activity, and lower educational levels were associated with T2DM among the Berber group. These findings suggest that the insulin receptor gene and lifestyle factors in combination may contribute to the occurrence of T2DM in the Berber portion of this island population.

Is serum transthyretin a reliable marker of nutritional status in patients with end-stage renal disease?

OBJECTIVE: To test the value of serum transthyretin (TTR) concentration as a nutritional marker in renal patients. METHODS: The study included 115 renal patients, out of which 35 are on conservative treatment, 50 on hemodialysis and 30 renal transplant recipients, and 31 healthy control subjects. Serum TTR, albumin, transferrin, C-reactive protein (CRP) and alpha1 anti trypsine (AAT) were assessed by immunoturbidimetry, and vitamin A by HPLC. Linear regression models were applied to test the association between serum TTR and body mass index (BMI). RESULTS: Serum TTR concentrations were normal, but serum vitamin A, CRP and AAT concentrations were significantly higher in patients. In renal patients, serum TTR was positively and independently related to BMI and was significantly lower in malnourished than well-nourished patients (367+/-91 vs. 417+/-130 mg/L; p=0.05). The risk of serum TTR<300 mg/L was higher in malnourished patients [OR, 4.82 (1.78-13.2); p=0.001]. CONCLUSION: Serum TTR concentrations were at normal range in renal patients despite evidence of malnutrition and inflammation. However, they were related to BMI and were significantly lowered in malnourished patients. Thus, serum TTR would reflect nutritional status in renal patients. However, the cutoff of malnutrition should be raised to 300 mg/L.