Clinical Pharmacokinetic and Pharmacodynamic Profile of Cinacalcet

[Archives Medical Review Journal 2014; 23(2.000): 362-365

Efficacy and safety of calcium acetate-magnesium carbonate in the treatment of hyperphosphatemia in dialysis patients

A phosphate binder combining calcium and magnesium offers an interesting therapeutic option to control hyperphosphatemia in dialysis patients. We investigated the effectiveness and tolerance of calcium acetate-magnesium carbonate (Ca-Mg). This is a 16-week prospective study including 16 dialysis patients. After an initial two-week washout period, serum phosphorus (sPho) ≥1.8 mmol/L, serum calcium (sCa) ≤2.6 mmol/L, and serum magnesium ≤1.5 mmol/L were the main inclusion criteria. The initial dose of Ca-Mg depended on sPho level and was titrated for every two weeks to have a sPho ≤ 1.8 mmol/L. A second two-week washout period followed the 12 weeks of treatment. Ca-Mg significantly reduced the mean sPho levels from 2.14 to 1.75 mmol/L by the end of the 12-week treatment period (P <0.006). Two weeks after the completion of the Ca-Mg study, the mean sPho levels increased to 2.2 mmol/L. The mean sCa levels did not significantly change during the Ca-Mg trial. The mean serum intact parathyroid hormone declined significantly from 446 pg/mL at the beginning of the study to 367 pg/mL at the end of the 12-week treatment period (P = 0.0002). Digestive tolerance was good in all patients which allowed good compliance. There were no episodes of hypercalcemia. However, six patients had a moderate hypermagnesemia (21 episodes) requiring adjustment of treatment dose. The Ca-Mg proved to be effective in the control of hyperphosphatemia in dialysis patients with good clinical and biological tolerance. Thus, in patients with hypercalcemia or poor tolerance to calcium carbonate, Ca-Mg might be a good alternative

Light chain nephropathy

Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypic immunoglobulin light chains of either kappa or lambda isotype. It is the archetypal systemic disease that is most frequently diagnosed on a kidney biopsy, although the deposits may involve several other organs. This brief review focuses on the clinicopathological features of LCDD-associated nephropathy with an emphasis on the diagnostic and therapeutic difficulties related to this elusive condition

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

Acute renal failure by ingestion of Euphorbia paralias

Euphorbia paralias is known in traditional medicine as an anti-inflammatory agent, a purgative and for its local anesthetic property. To the best our knowledge, renal toxicity of this substance has not been previously reported. In this paper, we report the case of a 29-year-old male who developed renal damage following ingestion of Euphorbia paralias. He had been on follow-up for nephrotic syndrome since 1986, although irregularly, with several relapses but each responding well to steroid therapy. A kidney biopsy had not been performed earlier due to refusal by the patient. He was off steroids since April 2008 because the patient developed osteoporosis. He was admitted with general malaise and oliguria to our department in May 2009, following repeated vomiting and watery diarrhea for three days. On examination, he was edematous but had normal vital signs except for a pulse rate of 120/min. Hemoglobin was only 5.5 g/dL but with normal white cell and platelet counts. Blood biochemistry showed evidence of advanced renal failure with a serum creatinine level of 1835 μmol/L and urea at 44.6 mmol/L, sodium of 132 μmol/L and potassium at 4.3 mmol/L. He had features of nephrotic syndrome with severe hypoproteinamia and 24-h urinary protein of 10.45 g. Ultrasonography revealed enlarged kidneys with a reduced echogenecity of the medulla and the papillae. Subsequently, after hemodialysis with blood transfusion, a kidney biopsy was performed that showed focal segmental glomerulosclerosis associated with an acute tubular injury. On intensive interrogation, the patient gave a history of ingesting boiled Euphorbia paralias as a native treatment for edema, ten days prior to the onset of the current illness. A diagnosis of acute renal failure (ARF) resulting from the possible nephrotoxic effect of Euphorbia paralias poisoning was made. He was treated with intermittent hemodialysis and corticosteroids. Serum creatinine values improved after 48 days. At six months following the intoxication, serum creatinine of the patient was 240 μmol/L. In cases of unexplained ARF, a toxic mechanism should always be considered and acute renal failure caused by Euphorbia paralias should be included as a cause if renal toxicity is suspected in those places where it is being used as a native medicine

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 (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

Acute rejection episodes after kidney transplantation

Acute rejection episodes (AREs) are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4&#x0025;) and 94 females (33.6&#x0025;), and their mean age was 31 &#x00B1; 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4&#x0025;. The incidence was &gt; 45&#x0025; between 1986 and 1997, decreased to 20.5&#x0025; between 1998 and 2000 and to 9&#x0025; between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91&#x0025; and 93&#x0025; at three years, 82&#x0025; and 90&#x0025; at five years and 73&#x0025; and 83&#x0025; at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population

Renal amyloidosis in ankylosing spondylitis: A monocentric study and review of literature

Secondary renal amyloidosis (RA) is the most common type of renal involvement in ankylosing spondylitis (AS). We assessed the epidemiologic and clinico-biological profile of AS patients with RA, to analyze treatment modalities and prognostic aspects, and to determine predictive factors of RA during AS. This was a retrospective study including 13 cases of RA among 212 cases who presented with AS, during the period from 1978 to 2006. The median age of the patients at the time of diagnosing AS was 47 years (range: 19–67). There were 11 males and two females. RA onset was diagnosed after a mean follow-up of 144.6 months (range: 10–505) from the AS diagnosis. We noted erosive peripheral arthritis, lumbar stiffness with bamboo spine, and coxitis in 23.1%, 76.9%, and 30.8% of cases, respectively. Nephrotic syndrome was found in eight patients (61.5%). At the time of diagnosing RA, six patients had renal failure. Amyloid deposits were histologically proven by salivary gland biopsy in six cases (46.1%) and by renal biopsy in seven cases (53.8%). Four patients received a long-course treatment with colchicine but with a good outcome only in two cases. In our series, AS was more severe among patients with RA. Four predictive factors of RA were identified: smoking (P = 0.04), erosive peripheral arthritis (P = 0.002), bamboo spine (P = 0.001), and biologic indicators of inflammation (P = 0.0001). High erythrocyte sedimentation rate was identified as the only independent risk factor of RA during AS (P = 0.0001). Renal function as well as urinalysis should be monitored at regular intervals to detect early renal involvement during AS

New familial cases of karyomegalic interstitial nephritis with mutations in the FAN1 gene

Abstract 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

Risk factors and consequences of delayed graft function

The impact of delayed graft function (DGF) on the outcome of renal transplantation remains controversial. We analyzed the risk factors for DGF and its impact on graft and patient survival. A total of 354 renal transplants performed between June 1986 and April 2000 were analyzed. Variables analyzed included donor and recipient age, method and duration of renal replacement therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute rejection, length of stay in the hospital, serum creatinine at the end of first hospitalization as well as graft and patient survival at one, three, five and ten years. The study patients were divided into two groups: patients with DGF (G1) and those without DGF (G2). DGF occurred in 50 patients (14.1%), and it was seen more frequently in patients transplanted from deceased donors (60% vs. 40%, P <0.0001). The cause of DGF was acute tubular necrosis, seen in 98% of the cases. Univariate analysis showed a statistically significant difference between the two groups G1 and G2 in the following parameters: average duration on dialysis (52.3 vs. 36.4 months, P = 0.006), HLA mismatch (44.9% vs. 32.11% P = 0.015), donor age (35.9 vs. 40.2 years, P = 0.026), cold ischemia time (23 vs. 18.2 h, P = 0.0016), warm ischemia time (41.9 vs. 38.6 mn, P = 0.046), length of stay in the hospital during first hospitalization (54.7 vs. 33.2 days, P <0.0001), serum creatinine at the end of first hospitalization (140 vs. 112 μmol/L, P <0.0001) and at three months following transplantation (159 vs. 119 μmol/L, P = 0.0002). Multivariate analysis revealed the following independent risk factors for DGF: deceased donor (RR = 13.2, P <0.0001) and cold ischemia time (RR = 1.17, P = 0.008). The graft survival at one, three, five and ten years was 100%, 93%, 88.3% and 78.3% in G1 versus 100%, 95.9% 92.8% and 82.3% in G2; there was no statistically significant difference. The patient survival at one, three, five and ten years was 100%, 91.3%, 83.6% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 with a statistically significant difference (P = 0.04). Prolonged cold ischemia time and transplantation of kidneys from deceased donors were the main risk factors for DGF in our study. Also, DGF significantly affected patient survival but had no influence on graft survival