Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients.

BACKGROUND: The effect of tacrolimus (TAC) on oxidative stress after kidney transplantation (KT) is unclear. This study aimed to evaluate the influence of TAC trough levels of oxidative stress status in Tunisian KT patients during the post-transplantation period (PTP). METHODS: A prospective study including 90 KT patients was performed. TAC whole-blood concentrations were measured by the microparticle enzyme immunoassay method and adjusted according to the target range. Plasma levels of oxidants (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)) and antioxidants (ascorbic acid, glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured using spectrophotometry. The subjects were subdivided according to PTP into three groups: patients with early, intermediate, and late PT. According to the TAC level, they were subdivided into LL-TAC, NL-TAC, and HL-TAC groups. RESULTS: A decrease in MDA levels, SOD activity, and an increase in GSH levels and GPx activity were observed in patients with late PT compared to those with early and intermediate PT (p < 0.05). Patients with LL-TAC had lower MDA levels and higher GSH levels and GPx activity compared with the NL-TAC and HL-TAC groups (p < 0.05). CONCLUSION: Our results have shown that in KT patients, despite the recovery of kidney function, the TAC reduced but did not normalize oxidative stress levels in long-term therapy, and the TAC effect significantly depends on the concentration used.

The presence of two light chain bands on immunofixation is associated with poor outcomes in newly diagnosed multiple myeloma patients.

We aimed to describe the clinical and biological characteristics and the prognosis of patients presenting with an additional light chain (LC) band along with a complete monoclonal protein on immunofixation (IF).An 8-year descriptive study was conducted to assess all cases with confirmed monoclonal gammopathies (MG). We studied those with an entire M-protein with 2 bands of LC of the same isotype based on the results of IF. Data were collected from patients' files.Among 548 cases of MG, we found 32 cases (5.8%) with an additional LC band. We included 28 patients (5%) with a confirmed diagnosis of multiple myeloma (MM). The m/f ratio was 2.5 with a median age of 63 years [32-80 years]. All MM patients had anemia, 16 (57%) had renal failure, 14 (50%) had lytic lesions, 9 (32%) received hemodialysis, and 7 (25%) had hypercalcemia. The free-kappa-lambda ratio was abnormal in all cases: median = 0.07 [0.002-58.57]. The mean overall survival (OS) was 22 months ± 38.76.Fifteen MM patients (48%) received chemotherapy, and 7 (22%) autologous stem cell transplants (SCT). Patients who received SCT had an OS higher than those who received other treatments (p = 0.038). OS was low in patients with high ß2microglobulin levels (rho = -0.791; p = 0.001), and abnormally low free-kappa-lambda ratio (rho = -0.852;p = 0.04).The presence of an additional LC band with a complete monoclonal protein seems to identify newly diagnosed MM patients with poor outcomes and frequent renal impairment.

Water implications in dialysis therapy, threats and opportunities to reduce water consumption: a call for the planet.

Water is a dwindling natural resource, and potable water is wrongly considered an unlimited resource. Dialysis, particularly hemodialysis, is a water-hungry treatment that impacts the environment. The global annual water use of hemodialysis is approximately 265 million m3/yr. In this reference estimate, two-thirds of this water is represented by reverse osmosis reject water discharged into the drain. In this review, we would like to draw attention to the complexity and importance of water saving in hemodialysis. We propose that circular water management may comply with the "3R" concept: reduce (reduce dialysis need, reduce dialysate flow, and optimize reverse osmosis performance), reuse (reuse wastewater as potable water), and recycle (dialysis effluents for agriculture and aquaponic use). Awareness and sustainability should be integrated to create positive behaviors. Effective communication is crucial for water savings because local perspectives may lead to global opportunities. Besides the positive environmental impacts, planet-friendly alternatives may have significant financial returns. Innovative policies based on the transition from linear to circular water management may lead to a paradigm shift and establish a sustainable water management model. This review seeks to support policymakers in making informed decisions about water use, avoiding wasting, and finding solutions that may be planet friendly and patient friendly in dialysis, especially in hemodialysis treatments.

Melatonin intake before intradialytic exercise reverses oxidative stress and improves antioxidant status in hemodialysis patients.

PURPOSE: The present study aimed to investigate for the first time the effects of melatonin (MEL) intake on oxidative stress and cellular damage during intradialytic exercise (IEX). METHODS: Thirteen hemodialysis (HD) patients volunteered to participate in the current randomized crossover trial. Participants performed four HD sessions in four different conditions: (Exercise (EX)-MEL), (EX-Placebo (PLA)), (Control (C)-MEL), and (C-PLA). 3 mg of MEL or PLA were taken 60 min before starting exercise, or at the equivalent time in the C conditions. Blood samples were taken before HD (T0), immediately after the end of IEX (T1), 60 min after IEX (T2), or at the corresponding times in the C conditions to measure free radicals damage, antioxidant biomarkers, as well as biomarkers of muscle and liver damage. RESULTS: Malondialdehyde and Advanced Oxidation Protein Products decreased in (C-MEL) (p < 0.05, d = 2.19; p < 0.01, d = 0.99, respectively) at T2 compared to T0. Catalase and total thiol levels increased in (C-MEL) (p < 0.01, d = 1.51; p < 0.01, d = 1.56, respectively) and in (EX-MEL) (p = 0.01, d = 1.28; p < 0.01, d = 1.52, respectively) at T1 compared to T0. Total bilirubin levels increased in (EX-MEL) and (C-MEL) at T2 compared to T0 (p < 0.001, d = 2.77; p < 0.001, d = 1.36, respectively), but only at T2 compared to T1 in (EX-MEL) (p < 0.001, d = 1.67). In all conditions, uric acid levels decreased at T1 compared to T0 and at T2 compared to T1, while biomarkers of muscle and liver damage remained unchanged. CONCLUSION: This pilot study is the first to show that MEL ingestion, alone or combined with IEX, could improve oxidant-antioxidant balance during HD.

Biclonal Gammopathies in South Tunisia: Clinical and Biological Characteristics.

OBJECTIVE: Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features. METHODS: We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. RESULTS: A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ±â€…10.87 years [range, 45-90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease. CONCLUSION: BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM.

Effects of intradialytic exercise in combination with melatonin supplementation on functional capacity, postural balance, and quality of life in hemodialysis patients.

INTRODUCTION: We evaluated the effect of intradialytic concurrent (resistance-endurance) training combined with melatonin (MEL) supplementation on functional capacity, muscle strength, postural balance, and quality of life (QoL) in hemodialysis (HD) patients. METHODS: Thirty-three HD patients were randomized into three groups: Exercise (EX)-MEL (n = 11); EX-Placebo (PLA) (n = 11) and Control (C)-PLA (n = 11). Participants included in the EX-MEL and EX-PLA groups were submitted to concurrent training for 12 weeks. RESULTS: EX-MEL and EX-PLA improved functional capacity, muscle strength, QoL, and postural balance parameters in eyes open and eyes closed conditions. Parameters of postural balance in the dual task condition were improved only in EX-MEL. EX-MEL induced better results in some domains of QoL compared with EX-PLA. CONCLUSION: Intradialytic concurrent training induced beneficial effects on physical function, muscle strength, postural balance, and QoL in HD patients. MEL supplementation combined with intradialytic exercise lead to better improvements in postural balance and QoL.

ePHex: a phase 3, double-blind, placebo-controlled, randomized study to evaluate long-term efficacy and safety of Oxalobacter formigenes in patients with primary hyperoxaluria.

BACKGROUND: Primary hyperoxalurias (PHs) are rare genetic diseases that increase the endogenous level of oxalate, a waste metabolite excreted predominantly by the kidneys and also the gut. Treatments aim to improve oxalate excretion, or reduce oxalate generation, to prevent kidney function deterioration. Oxalobacter formigenes is an oxalate metabolizing bacterium. This Phase III, double-blind, placebo-controlled randomized trial investigated the effectiveness of orally administered Oxabact™, a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH. METHODS: Subjects (≥ 2 years of age) with a diagnosis of PH and maintained but suboptimal kidney function (mean estimated glomerular filtration rate at baseline < 90 mL/min/1.73 m2) were eligible to participate. Subjects were randomized to receive Oxabact or placebo twice daily for 52 weeks. Change from baseline in plasma oxalate concentration at Week 52 was the primary study endpoint. RESULTS: Forty-three subjects were screened, 25 were recruited and one was discontinued. At Week 52, O. formigenes was established in the gut of subjects receiving Oxabact. Despite decreasing plasma oxalate level in subjects treated with Oxabact, and stable/increased levels with placebo, there was no significant difference between groups in the primary outcome (Least Squares mean estimate of treatment difference was - 3.80 µmol/L; 95% CI: - 7.83, 0.23; p-value = 0.064). Kidney function remained stable in both treatments. CONCLUSIONS: Oxabact treatment may have stabilized/reduced plasma oxalate versus a rise with placebo, but the difference over 12 months was not statistically significant (p = 0.06). A subtle effect observed with Oxabact suggests that O. formigenes may aid in preventing kidney stones. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acinetobacter lwoffi peritonitis in peritoneal dialysis: two cases report.

Peritonitis is an important cause of morbidity and technique failure in peritoneal dialysis. Herein, we report peritonitis related to Acinetobacter lwoffi in two patients on peritoneal dialysis. The first case is a 63-year-old patient treated by automated peritoneal dialysis admitted with abdominal pain. The peritoneal effluent White Blood Cells count consisted of 280 cells/mm3. Then culture identified a multisensitive Acinetobacter lwoffi. Treatment with ceftazidime and ciprofloxacin had been started. The control dialysate culture was sterile after three weeks. The second patient is a 59-year-old female admitted because of diffuse abdominal pain and cloudy dialysate. The peritoneal effluent White Blood Cells count consisted of countless leukocytes, with predominantly polynuclear and culture identified Acinetobacter lwoffi. He received intraperitoneal ceftazidim and amikacin for three weeks. The control dialysate was sterile. Acinetobacter lwoffi is a rare cause of peritonitis and it can be treated successfully with early recognition and appropriate antibiotic therapy based on culture instead of catheter removal.

Chronic Kidney Disease, Hypokalemia, and Appendicular Mucocele in a 66-Year-Old Man.

Appendicular mucocele (AM) is a rare and potentially malignant entity linked to obstructive dilatation of the appendix with an intraluminal accumulation of mucoid material. Most AM is asymptomatic or simulates acute appendicitis. We report an exceptional case of AM discovered in the face of hypokalemia and aggravation of chronic kidney disease (CKD) without diarrhea in an old man. Investigations led to the diagnosis of AM in its malignant form complicated by gelatinous ascites. We retained mucinous hypersecretion as the cause of hypokalemia and acute renal failure. Aggressive surgery and intraperitoneal chemotherapy corrected hydroelectrolyte imbalance.

Bone marrow aspirate: a diagnostic tool for primary hyperoxaluria type 1.

INTRODUCTION: Type1 primary hyperoxaluria is an infrequent autosomal recessive metabolic disease characterized by the accumulation of calcium oxalate in the kidney, which leads to end stage renal disease. In fact, the diagnosis of this disease is mandatory in order to avoid graft loss. AIM: To assess the incidence of primary hyperoxaluria and to develop the diagnostic value of bone marrow infiltration by calcium oxalate in uremic stone former patients. METHODS: This study was conducted on a cohort of stone former patients identified in the south of Tunisia over a period of 18 years. Baseline characteristics were recorded. Clinical and laboratory data were collected on chart review. Secondary forms of hyperoxaluria were excluded. Bone marrow aspirate was performed in uremic patients from this cohort because early hyperoxaluria was suspected. Diagnostic accuracy of this test relating to sensitivity, specificity, positive predictive value and negative predictive value were also calculated. RESULTS: A cohort of 31 patients comprising 17 male patients and 14 female patients were identified. During this time of diagnosis, the patient's ages ranged from 9 to 57 years old and 22 of them (70%) unfortunately died. Bone marrow aspirate was safely done in 16 uremic patients. It was positive in 12 patients and negative in 4 patients. Sensitivity, specificity, positive predictive value and negative predictive value were respectively 85%, 100%, 100% and 50%. CONCLUSION: The bone marrow examination represents both an easy and a worldwide feasible solution for the diagnosis of oxalosis, which affords an early diagnosis.

Next-generation sequencing in patients with familial FSGS: first report of collagen gene mutations in Tunisian patients.

Focal segmental glomerulosclerosis (FSGS) is a histological lesion with many causes, including inherited genetic defects, with significant proteinuria being the predominant clinical finding at presentation. FSGS is considered as a podocyte disease due to the fact that in the majority of patients with FSGS, the lesion results from defects in the podocyte structure. However, FSGS does not result exclusively from podocyte-associated genes. In this study, we used a genetic approach based on targeted next-generation sequencing (NGS) of 242 genes to identify the genetic cause of FSGS in seven Tunisian families. The sequencing results revealed the presence of eight distinct mutations including seven newly discovered ones: the c.538G>A (p.V180M) in NPHS2, c.5186G>A (p.R1729Q) in PLCE1 and c.232A>C (p.I78L) in PAX2 and five novel mutations in COL4A3 and COL4A4 genes. Four mutations (c.209G>A (p.G70D), c.725G>A (p.G242E), c.2225G>A (p.G742E), and c. 1681_1698del) were detected in COL4A3 gene and one mutation (c.1424G>A (p.G475D)) was found in COL4A4. In summary, NGS of a targeted gene panel is an ideal approach for the genetic testing of FSGS with multiple possible underlying etiologies. We have demonstrated that not only podocyte genes but also COL4A3/4 mutations should be considered in patients with FSGS.

Melatonin ingestion before intradialytic exercise improves immune responses in hemodialysis patients.

PURPOSE: The present study aimed to investigate the effects of melatonin (MEL) intake on systemic inflammation and immune responses during intradialytic exercise. METHODS: Thirteen hemodialysis (HD) patients volunteered to participate in the current randomized-crossover study. Immunological responses were monitored in four HD sessions at different conditions: [Exercise (EX) + MEL], [EX + Placebo (PLA)], [Control (CON) + MEL] and [CON + PLA]. MEL (3 mg) or PLA was ingested 1 h before starting exercise or the equivalent time in CON condition. During all sessions, peripheral blood samples were collected to assess c-reactive protein, complete blood count, and immune cells phenotypes before HD (T0), immediately after exercise (T1) and 1 h after exercise (T2) or at corresponding times in the CON condition. RESULTS: HD therapy induced a significant decrease in natural killer (NK) (p = 0.001, d = 0.85; p < 0.001, d = 1.19, respectively) and CD8+ T-lymphocytes rates (p = 0.001, d = 0.57; p < 0.001, d = 0.75, respectively) at T1 and T2 compared to T0. MEL intake prevented the decrease in NK and CD8+ T-lymphocytes, increased the proportion of CD4+ T-lymphocytes at T1 and T2 compared to T0 (p = 0.002, d = 1.18; p = 0.001, d = 1.04, respectively) and decreased the proportion of CD14++CD16+ Monocytes at T2 compared to T0 (p = 0.02, d = 1.57) in peripheral blood during HD therapy. Similar results were found in [EX + MEL] and [EX + PLA] conditions. CONCLUSION: This pilot study provides the first evidence that MEL intake alone or associated with intradialytic exercise displays potential immunoregulatory and anti-inflammatory effects. The combination of MEL with intradialytic exercise may be an appropriate anti-inflammatory therapy for HD patients.

[Urolithiasis of the kidney transplanted patient in south Tunisia: A 17-year experience]. / La lithiase urinaire du transplanté rénal dans le sud tunisien : expérience de 17 ans.

INTRODUCTION: Urolithiasis in a kidney transplanted patient is an uncommon but complex urological complication. Its potential severity comes from its occurrence on a solitary kidney and on a field of immunosuppression. The aim of our study is to assess the incidence, characteristics and course of urolithiasis in our series. METHODS: A retrospective study was performed. We included kidney transplanted patients between November 2002 and November 2019 and presenting lithiasis during their follow-up. Clinical, biological and radiological data were collected as well as lithiasis disease related data. The management of and patient's evolution were also specified. RESULTS: Seven of 416 kidney transplanted patients developed lithiasis during their follow-up with an incidence of 1.6 %. The mean age at lithiasis diagnosis was 36.5 years [24-55 years], the sex ratio was 1.3. They developed stones after mean follow-up of 67 months [4-168 months]. The stones' size varied from 2 to 18mm. Treatment was alkalisation in 3 cases, extracorporeal lithotripsy in 2 cases, a double J stent in 3 cases and pyelolithotomy in 2 cases. Four patients had multiple treatments. Three patients had 1 residual stone during evolution (7mm average diameter), 1 microlithiasis, 1 lost to follow-up after treatment and only 2 (out of 7) were "stone free". Furthermore, lithiasis didn't damage the graft survival after a median follow-up of 62 months post-treatment. CONCLUSION: Urolithiasis in the kidney transplanted patient requires an adapted multidisciplinary management. Its skill is a challenge for both the nephrologist and urologist.

Ciprofloxacin-induced crystal nephropathy.

Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug.

Cutaneous abnormalities in patients with end stage renal failure on chronic hemodialysis. A study of 458 patients.

BACKGROUND: Cutaneous manifestations occurring in patients with end stage renal failure on hemodialysis are polymorphic and diverse. OBJECTIVE: The aim of our study was to assess the prevalence and characteristics of different cutaneous manifestations in patients on hemodialysis. PATIENTS AND METHODS: We led a transverse investigation of all patients on hemodialysis in 12 haemodialysis centres of Sfax (Tunisia). We examined 458 patients (254 men and 204 women). The hemodialysis history ranged from 6 months to 24 years. A total of 394/458 (86%) patients had cutaneous abnormalities. These included pruritus (56.6% of patients), paleness (60.7%), xerosis (52.8%), hyperpigmentation or hypopigmentation (38.4%), venous dilation near the fistula (22.2%), eczema in the fistula area (14.8%), half-and-half nails (13.5%), onychodystrophy (6.1%), subungual hemorrhage (4.5%), leukonychia (4.5%), stomatitis (5.6%), xerostomia (3.2%), gingivitis (2.4%), uremic breath (2.1%), and skin calcificatins (0.4%). Nephrogenic fibrosing dermopathy was not detected in any of our patients. CONCLUSIONS: Pruritus, paleness, dry skin as well as hyperpigmentation and hypopigmentation are the most frequent skin abnormalities observed in hemodialysis patients. The early recognition of some cutaneous conditions associated with end stage renal failure and hemodialysis may allow early therapeutic intervention and decrease morbidity.

[Prospective observational study of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with chronic renal failure]. / Étude prospective observationnelle des hyperkaliémies secondaires aux inhibiteurs de l'enzyme de conversion chez des patients ayant une maladie rénale chronique hospitalisés.

OBJECTIVE: To study the incidence and risk factors of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with hypertension and preexisting chronic renal failure. METHODOLOGY: Two-months prospective observational study was used including all hospitalized patients older than 18 years with a history of hypertension, non-dialyzed chronic renal failure and who had angiotensin converting enzyme prescription at the time of the admission. Hyperkalemia greater than or equal to 5 mmol/L was detected in these patients. The studied variables were demographic, clinical, biological and therapeutic. RESULTS: Eight patients, among 27 included, had a hyperkalemia (2963%). They were 73±15 years old. Factors that predispose to hyperkalemia were present in all patients. Hyperkalemia was associated in six cases with decompensation of renal function. The age was associated with hyperkalaemia in patients treated with angiotensin converting enzyme inhibitors (RC=1.21; IC95 1,11-1,46; P=0,021). Diabetes is a possible risk factor (OR=59 021 et, 95 0.93 to 2410, P=0.053). Compared with patients who did not develop hyperkalemia, the occurrence of hyperkalemia in patients included was associated with a longer duration of hospitalization (OR=130, 95 112 to 160, P=0. 022). CONCLUSION: The prescription of angiotensin converting enzyme inhibitors in the elderly with chronic renal failure and diabetes requires careful monitoring of serum potassium.

Can we improve diagnosis of renal failure? A revised coding system for Middle East and North Africa.

INTRODUCTION: Reporting data on primary renal disease (PRD) causing end-stage renal failure (ESRF) is generally inconsistent and diagnostic groups poorly defined. METHODS: We have identified all papers published from the Eastern Mediterranean, Middle East, Arabia and North Africa during the decade 2000-2009 that report data on PRD in patients reaching ESRF in this region. RESULTS: We propose a system in which all diagnoses fall into one of 8 broad groups: ESRF of uncertain etiology, Congenital abnormalities of the kidney and urinary tract (CAKUT) and acquired Uropathy, Glomerular diseases, Tubulo-interstitial disease (TID), Other Congenital and Familial diseases, Diabetes, Renovascular disease, Other Specified Diagnoses. Each group has sub-headings, for instance, primary glomerulonephritis, secondary glomerulonephritis, and hereditary glomerular disease. And then for each sub-heading there is list of specific diagnoses similar to that used by EDTA and USRDS coding systems. We also recommend that 'etiology unknown' group should be reported in more detail as either 'glomerular phenotype' or 'tubular phenotype' and careful attention paid to evidence for a family history of renal disease. To improve reporting, all patients who are diabetic, and all who have evidence of familial inheritance, should be recorded and then a diagnostic category should also be chosen. So a diabetic patient is designated as 'diabetic nephropathy' only if they fulfil the case definition for that diagnosis. CONCLUSION: We know that collecting PRD data can be done much better as we have the example of the pediatric community which collects data that is very consistent, and has a low rate of 'unknown disease'.

[Takayasu arteritis in southern Tunisia: a study of 29 patients]. / Maladie de Takayasu au sud tunisien: étude de 29 cas.

OBJECTIVES: This study aimed to assess the clinical, laboratory, and radiological features and course of Takayasu arteritis in Tunisia. METHODS: This retrospective study analyzed 29 patients with Takayasu arteritis between 1996 and 2006 who met the criteria for inclusion proposed by the American College of Rheumatology (ACR). RESULTS: The file review identified 25 women and 4 men, with a mean age at diagnosis of 35.4 years (range: 18-65 years). Our series included 93% with involvement of the aortic arch and its branches, while only 24% involved renal arteries and 21% the abdominal aorta. We had no case with cardiac or pulmonary involvement. In all, 67.7% had type I disease, 10.7% type IIb, 3.6% type IV and 25% type V. Hypertension was recorded in 38%. No tuberculosis was observed. In all, 22 patients (75.8%) had glucocorticoid treatment, and 5 (17.2%) needed immunosuppressive therapy. Two patients with renal artery stenosis had endoluminal angioplasty and four patients (13.7%) required surgical intervention. Our patients were followed for a mean period of 80 months. Disease remained stable in 18 patients (64.2%). CONCLUSION: The clinical manifestations, angiographic data and course of our patients were similar to those in other reported series. We found no relation between Takayasu arteritis and tuberculosis.