Outcomes Following Surgical Interventions for Isolated Lunotriquetral Interosseous Ligament Injuries: A Systematic Review.

Ulnar-sided wrist pain can be attributed to various bony and ligamentous structures. The purpose of this review is to compare outcomes following surgical interventions for isolated lunotriquetral (LT) interosseous ligament injuries in adults. We assessed 202 procedures from 9 retrospective case series studies of low to moderate quality based on the Structured Effectiveness Quality Evaluation Scale. The comparative outcomes (ie, range of motion, pain, strength, quality of life, complications, return to work, and patient satisfaction) were aggregated and categorized under arthrodesis, capsulodesis, ligament repairs and reconstruction, and ulna shortening osteotomy procedures. Although the comparison of outcomes was largely inconclusive due to the heterogeneity and the omission of preoperative characteristic data, we did observe higher complications and reoperation rates post LT arthrodesis. It is recommended that all outcomes be standardized and presented uniformly with best practices developed to better characterize the injury's severity and integrity in future studies.

Extensive emphysematous pyelonephritis in a renal allograft treated conservatively: case report and review of the literature.

Emphysematous pyelonephritis (EPN) is a rare occurrence in renal allografts. An aggressive approach resulting in transplant nephrectomy is viewed as the standard of care. Over the recent years, treatment with percutaneous drainage (PCD) of the renal and perinephric collections and appropriate antibiotics has been reported with good success in lesser grades of this infection. Only 4 cases of extensive EPN disease with Escherichia coli, treated with conservative management, are reported in the English-language literature. We present a case of severe EPN caused by Klebsiella pneumoniae, successfully managed with early PCD, and propose a step-up strategy aimed toward graft preservation.

Relationship of Creatinine and Cystatin C-based Estimated Glomerular Filtration rates with Measured Glomerular Filtration Rate in Healthy Kidney Donors from South Asia.

Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation is currently recommended for the estimation of glomerular filtration rate (GFR). This retrospective study aimed to evaluate the correlation between creatinine and cysC-based estimated GFRs and measured GFR in healthy adults. Consecutive healthy adults who were accepted as voluntary kidney donors at our center between January 2008 and December 2012 were included in the study. The 336 individuals who comprised the study population had a mean age of 41.6 ± 11.8 years, male:female ratio 1:1.7, mean creatinine 0.9 ± 0.1 mg/dl, and mean cysC 0.8 ± 0.1 mg/dl. Mean measured GFR by Tc-99m diethylenetriaminepentaacetic acid using Gates method was 98.4 ± 21.2 ml/min/1.73 m2. The mean ± standard deviation of eGFRs by various formulae were as follows: Cockcroft-Gault (CG) = 88.1 ± 15.9 ml/min/1.73 m2, Modification of Diet in Renal Disease (MDRD) = 78 ± 14.7 ml/min/1.73 m2, CKD-EPI creatinine = 88.1 ± 15.5 ml/min/1.73 m2, CKD-EPI cysC = 97 ± 19.9 ml/min/1.73 m2, CKD-EPI creatinine-cysC (CKD-EPI cr-cysC) = 92.5 ± 14.1 ml/min/1.73 m2. The CKD-EPI cr-cysC equation had the highest accuracy, with 43% and 72% of values lying within ±10% and ±20% of the measured GFR, respectively. Bland-Altman analyses for levels of agreement showed least bias with CKD-EPI cysC overall and among females, while among males, CKD-EPI creatinine equation had the least bias. The CKD-EPI equation showed a higher performance than the MDRD and CG equation in GFR estimation of a healthy population. Among CKD-EPI equations, CKD-EPI cr-cysC had the highest accuracy and CKD-EPI cysC the least bias.

Pre-tertiary hospital care of patients with chronic kidney disease in India.

BACKGROUND & OBJECTIVES: There is paucity of data available on how chronic kidney disease (CKD) is treated before referral to a tertiary hospital. This study was conducted to assess pre-tertiary hospital care of patients with CKD 5 at their presentation to nephrology services at a tertiary care hospital. METHODS: Over a period of 8 months, consecutive patients with CKD 5 presenting at the Nephrology services at Christian Medical College, Vellore, Tamil Nadu, and their relatives were interviewed to assess the pre-tertiary hospital care and knowledge about CKD 5 and its treatment. RESULTS: A total of 561 patients with CKD 5 were enrolled. The mean duration (months) of known CKD was 12.4 +/- 23.1 and known CKD 5 was 3.2 +/- 3.5. Of these, 369 patients (65.8%) had been under the care of a nephrologist; 305 patients had CKD 5 as the initial presentation of renal illness. Vaccination against hepatitis B had been initiated in only 133 patients (23.7%). Only 172 patients(38%) had an adequately controlled blood pressure. Care under a nephrologist was more likely to result in appropriate investigation, treatment and patient education though blood pressure control did not differ. INTERPRETATION & CONCLUSION: Paucity of symptoms in the initial stages of certain forms of CKD probably led to 50 per cent of patients presenting with CKD 5 as the initial presentation of renal disease. Inadequate vaccination against hepatitis B infection highlights the need for appropriate vaccination. Prevention of CKD and its progression are important targets which requires physician awareness at all levels. Early referral to a nephrologist's care is more likely to result in appropriate investigations and treatment.

Infections with atypical mycobacteria in renal transplant recipients.

Infections due to atypical mycobacteria are infrequent in renal transplant recipients but they cause serious morbidity. These pathogens are common in patients with acquired immune deficiency syndrome (AIDS). We report four proven cases of infections caused with atypical mycobacteriae from 1997 to 2003, by different organisms namely, M. chelonei, M.fortuitum, M. abcessus and M. terrae in renal transplant recipients. Infection with M. terrae documented here is the first occurrence in a renal transplant patient. Histopathological examination of aspirates or biopsy specimens from involved areas and staining and culture for mycobacteriae are essential for diagnosis. Treatment involves antimycobacterial therapy, reduction in immunosuppression and surgery, if indicated. Atypical mycobacterial infections, though currently uncommon, are significant and could prove to be an emerging pathogen in renal transplant recipients in the context of the AIDS epidemic in India.

Spectrum of severe chronic kidney disease in India: a clinicopathological study.

BACKGROUND: The healthcare burden due to chronic kidney disease has increased worldwide in the past decade. Elucidating the aetiology of chronic kidney disease may help in identifying strategies for prevention, both in the population and the Individual patient. Only a clinicopathological study can define the exact spectrum of chronic kidney disease since epidemiological studies have not shown a consistent aetiological profile. The histological evidence used to support the diagnosis varies with the degree to which renal biopsy is done. Renal biopsy is the gold standard in making an aetiological diagnosis in renal failure, but as a diagnostic tool in chronic kidney disease it is underutilized. METHODS: This prospective study done at Christian Medical College, Vellore in southern India from 1998 to 2003 aimed to determine the aetiological profile of severe chronic kidney disease by analysing renal biopsies. The value of pre-renal biopsy clinical Judgement in predicting the histological diagnosis was also assessed. Patients with diabetic nephropathy were excluded from the study. RESULTS: Four hundred and fifty-seven patients had evidence of chronic kidney disease as evidenced on biopsy as well as on clinical parameters. Three hundred and twenty-two of these patients (70.5%) had glomerulonephritis as the histological diagnosis. Fifty-five (12%) had Interstitial nephritis, 30 (6.6%) had hypertensive arteriosclerosis and 28 (6.1%) had metabolic nephropathies. The positive predictive value of a pre-biopsy clinical diagnosis in predicting interstitial nephritis was very low (33%). A large number of patients clinically diagnosed to have chronic interstitial nephritis had other aetiologies of chronic kidney disease. CONCLUSION: Glomerulonephritis was the most common cause of chronic kidney disease, not including diabetic nephropathy, followed by interstitial disease and benign arterionephrosclerosis. In patients with unidentified severe chronic kidney disease, renal biopsy provided an aetiological diagnosis.

An integrated hybrid microfluidic device for oviposition-based chemical screening of adult Drosophila melanogaster.

Chemical screening using Drosophila melanogaster (the fruit fly) is vital in drug discovery, agricultural, and toxicological applications. Oviposition (egg laying) on chemically-doped agar plates is an important read-out metric used to quantitatively assess the biological fitness and behavioral responses of Drosophila. Current oviposition-based chemical screening studies are inaccurate, labor-intensive, time-consuming, and inflexible due to the manual chemical doping of agar. In this paper, we have developed a novel hybrid agar-polydimethylsiloxane (PDMS) microfluidic device for single- and multi-concentration chemical dosing and on-chip oviposition screening of free-flying adult stage Drosophila. To achieve this, we have devised a novel technique to integrate agar with PDMS channels using ice as a sacrificial layer. Subsequently, we have conducted single-chemical toxicity and multiple choice chemical preference assays on adult Drosophila melanogaster using zinc and acetic acid at various concentrations. Our device has enabled us to 1) demonstrate that Drosophila is capable of sensing the concentration of different chemicals on a PDMS-agar microfluidic device, which plays significant roles in determining oviposition site selection and 2) investigate whether oviposition preference differs between single- and multi-concentration chemical environments. This device may be used to study fundamental and applied biological questions in Drosophila and other egg laying insects. It can also be extended in design to develop sophisticated and dynamic chemical dosing and high-throughput screening platforms in the future that are not easily achievable with the existing oviposition screening techniques.

A prospective evaluation of leflunomide therapy for cytomegalovirus disease in renal transplant recipients.

AIM: A preliminary observation suggests leflunomide is effective in the treatment of cytomegalovirus (CMV) disease in renal transplant recipients. A prospective evaluation was conducted in renal transplant recipients to study the efficacy of leflunomide in the treatment of CMV disease. PATIENTS AND METHODS: With prior approval and informed consent for therapy and follow-up, 17 consecutive consenting renal transplant recipients with proven CMV disease were treated with leflunomide. CMV disease was defined as a clinical syndrome of fever and/or symptoms of organ involvement, leukopenia, and a positive nested CMV quantitative PCR test at 0.001 microg/5 microL template input, with or without histologic evidence of tissue invasion. Leflunomide metabolite concentrations (A77 1726) were monitored. RESULTS: Of the 17 patients, 14 patients were treated for 6 months for CMV disease the first time; the remaining 3 received leflunomide treatment for relapse after ganciclovir treatment, for a year. Seven patients had fever with viremia and no organ involvement, nine had viremia with involvement of gastrointestinal tract, and one had fever with CMV inclusions in the allograft, with no demonstrable viremia. The three patients with relapse treated with leflunomide responded. Overall, 15 patients (88%) clinically responded to leflunomide therapy and with viral clearance from blood and healing of involved organs. The cost of therapy with intravenous ganciclovir (Cymevene, Roche) for 2 weeks was US 721 dollars while that of leflunomide (Cleft, Cipla Ltd) for 6 months was US 64 dollars. CONCLUSION: Leflunomide treatment for CMV disease in renal transplant recipients is effective, simple, and economical.

Adefovir nephrotoxicity in a renal allograft recipient.

Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV) infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN) were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

Agar-polydimethylsiloxane devices for quantitative investigation of oviposition behaviour of adult Drosophila melanogaster.

Drosophila melanogaster (fruit fly) is a model organism and its behaviours including oviposition (egg-laying) on agar substrates have been widely used for assessment of a variety of biological processes in flies. Physical and chemical properties of the substrate are the dominant factors affecting Drosophila's oviposition, but they have not been investigated precisely and parametrically with the existing manual approaches. As a result, many behavioral questions about Drosophila oviposition, such as the combined effects of the aforementioned substrate properties (e.g., exposure area, sugar content, and stiffness) on oviposition and viability, and their threshold values, are yet to be answered. In this paper, we have devised a simple, easily implementable, and novel methodology that allows for modification of physical and chemical composition of agar substrates in order to quantitatively study survival and oviposition of adult fruit flies in an accurate and repeatable manner. Agar substrates have been modified by surface patterning using single and hexagonally arrayed through-hole polydimethylsiloxane (PDMS) membranes with various diameters and interspacing, as well as by substrate stiffness and sugar content modification via alteration of chemical components. While pure PDMS substrates showed a significant lethal effect on flies, a 0.5 mm diameter through-hole access to agar was found to abruptly increase the survival of adult flies to more than 93%. Flies avoided ovipositing on pure PDMS and on top of substrates with 0.5 mm diameter agar exposure areas. At a hole diameter of 2 mm (i.e., 0.25% exposure area) or larger, eggs were observed to be laid predominately inside the through-holes and along the edges of the PDMS-agar interface, showing a trending increase in site selection with 4 mm (i.e., 1% exposure area threshold) demonstrating natural oviposition rates similar to pure agar. The surface-modified agar-PDMS hybrid devices and the threshold values reported for the substrate physical and chemical conditions affecting oviposition are novel; therefore, we advocate their use for future in-depth studies of oviposition behaviour in Drosophila melanogaster with accuracy and repeatability. The technique is also useful for development of novel assays for learning and decision-making studies as well as miniaturized devices for self-assembly of eggs and embryonic developmental investigations.

Preemptive live-related renal transplantation.

BACKGROUND: Preemptive transplantation (PTX) utilizes transplantation as the primary renal replacement therapy in the absence of any preceding dialysis. In developing countries, PTX may be a cost-effective option, offering additional benefits to conventional transplantation. METHODS: Between 1989 and 1996, 43 patients who underwent live-related PTX were compared with 86 matched controls who underwent transplantation after hemodialysis. Pre- and posttransplant morbidity, and graft and patient survival rates were compared. RESULTS: Median follow-up was 15 months in the preemptive group and 20.5 months in the control group. Controls received more transfusions (4.6+/-2.6 vs. 2.4+/-2.3), had higher hepatitis B surface antigen positivity [12 (14.6%) vs. 1 (2.4%)], and more commonly had hepatic dysfunction [5 (5.8%) vs. nil)] in the pretransplant period compared with the preemptive group. Similarly, at 6 months after transplant, the incidence of hepatitis B surface antigen positivity (13 vs. 2) and hepatic dysfunction (18 vs. 3) were higher in the control group compared with the preemptive group. The 1- and 2-year graft (preemptive: 82.8% and 77.3%; controls: 82% and 78%, respectively) and patient (preemptive: 92% and 89.5%; controls: 91% and 89.5%, respectively) survival rates were similar. CONCLUSION: PTX offers comparable patient and graft survival to conventional transplantation. It eliminates the complications and inconvenience of dialysis. Transfusion requirements, and therefore associated morbidity, are lower. PTX is more cost effective, therefore, it should be a recommended practice in a developing country.

Gastric aspiration for diagnosis of pulmonary tubercolosis in adult renal allograft recipients.

Of 213 renal allgraft recipients suspected to have had pulmonary tuberculosis, 132 had sputum examinations and 14 showed acid-fast bacilli. Of the remaining 118 patients, 25 had gastric aspirations, 18 had bronchoalveolar lavage, and 75 did not require further investigation because of spontaneous improvement or confirmation of an alternative diagnosis. While 9 of the 25 patients' gastric aspirate examination was positive, all the 18 who had bronchoalveolar lavage were negative for acid-fast bacilli. Eighty-one patients without expectoration had gastric aspiration directly and 14 showed acid-fast bacilli. Of the remaining 67 patients only 17 had bronchoalveolar lavage, of which three were positive for AFB and the rest did not require further testing for tuberculosis. A total of 106 patients had gastric aspiration. Acid-fast bacillus positivity was significantly more (P<.01) in patients with abnormal chest radiographs as compared with patients with normal chest radiographs as compared with patients with normal chest radiograph results. We suggest gastric aspiration for AFB in all renal transplant recipients who have fever, scanty expectoration, and abnormal chest radiograph with clinical suspicion of pulmonary tuberculosis.

The effect on patient management of temporary non-availability of immunofluorescence for renal biopsy reporting.

Delay in reporting the immunofluorescence findings on renal biopsies, owing to an interruption in supply of reagents, made possible a retrospective analysis of the effect of the lack of this information on patient management. Hospital case records of the 39 patients so affected were reviewed to determine what changes in their management took place after the immunofluorescence findings became available. The clinical, laboratory, and light microscopic findings in all except a case of pauci-immune crescentic glomerulonephritis allowed management decisions to be made that were not influenced by immunofluorescence findings. This was owing to correct prediction of the immunofluorescence findings, as in cases of IgA nephropathy presenting with recurrent haematuria; the adequacy of light microscopy in the interpretation of graft biopsies, in classifying lupus nephritis and in most cases of nephrotic syndrome; and the absence of entities identifiable only by immunofluorescence among these patients.

Low prevalence of hepatitis D (delta) virus infection in a nephrology unit in south India.

Fifty-five consecutive patients with end-stage renal disease entering haemodialysis programmes over a two-month period and 48 consecutive recipients of renal allografts during a period of 6 months were investigated for hepatitis B virus (HBV) and hepatitis D virus (delta) infection. HBV markers were present in 25 of the former and 40 of the latter. Of the 65 patients with HBV infection, 12 were not available for delta antibody screening. HBV infection was present for a mean of 2.5 months and 45.3% of those infected had clinical hepatitis; none had fulminant hepatitis. All the patients tested were negative for antidelta antibody. An additional patient on dialysis with delta superinfection and hepatic encephalopathy is also reported.

Leprosy and renal transplantation.

Nine cases of leprosy in patients treated at a large renal transplant centre in South Asia are described. Three had leprosy diagnosed before transplantation and had either completed or were continuing chemotherapy at the time of transplantation. One showed exacerbation of undisclosed leprosy after transplantation. Five patients developed the disease for the first time 22 months to 12 years after transplantation. Immunosuppression did not adversely affect the treatment of leprosy in any of the patients though concurrent liver disease required cessation of rifampicin in one patient.

Free radical injury in human renal allograft rejection.

Plasma and renal tissue levels of lipid peroxide and plasma vitamin E were estimated as measures of free radical injury in five renal allograft recipients with untreated and four with unsuccessfully treated acute cellular rejection and compared with 11 control patients with minimal change disease. Plasma lipid peroxide was significantly higher in patients studied before antirejection therapy (13.2 +/- 3.5 nmol/ml; P < 0.01) as well as in those after unsuccessful antirejection treatment (11.7 +/- 0.7 nmol/ml; P < 0.01), compared to controls (5.7 +/- 2.8 nmol/ml). Levels of plasma vitamin E and renal tissue lipid peroxide were similar in both groups, however the latter was significantly raised in patients evaluated prior to antirejection therapy than in those after unsuccessful antirejection therapy (5.1 +/- 1.7 and 3.0 +/- 0.8 nmol/mg protein; P < 0.05). These findings suggest possible free radical mediated injury during renal allograft rejection.

Role of molecular techniques in the detection of HBV DNA & HCV RNA among renal transplant recipients in India.

In this study we have investigated the occurrence of hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) infections among 68 renal transplant recipients. Replicative HBV and replicative HCV infections were seen in 12 (17.6%) and 38 (55.9%) patients respectively, the difference was statistically significant (P < 0.001). Among the 38 HCV RNA+ individuals, anti-HCV was present only in 23. Anti-HCV in the absence of HCV RNA was detected in one patient. Anti-HDV antibody was seen in 2 (15.4%) of the 13 HBV infected individuals. Nine (13.2%) of the 68 individuals had replicative dual infection with HBV and HCV. Triple infection (HBV DNA+, HCV RNA+, anti-HDV+) was seen in 2 transplant recipients. There was significantly higher demonstration of replicative HCV (P < 0.001) in transplant recipients having elevated liver enzymes (n = 34) as compared to transplant recipients having normal liver enzyme levels (n = 34). Though not significant, a higher detection rate was also seen with replicative HBV infection and replicative dual infection among transplant recipients with elevated liver enzymes. The higher detection of HCV in renal transplant recipients by molecular techniques, emphasizes the need for HCV RNA testing. Further deliberate attempts to change practices to reduce this problem may also improve graft and patient survival in recipients.

Characterization of antibody response to human cytomegalovirus in Indian renal transplant patients.

BACKGROUND & OBJECTIVES: Cytomegalovirus (CMV) disease in seroendemic transplant populations is due to reactivation of the virus, or reinfection. In this context, the antibody response is likely to influence presentation, clinical severity and outcome of the disease, and may provide a diagnostic and prognostic marker. This study was carried out in Indian renal transplant patients and healthy adults to characterize the antibody response to cytomegalovirus. METHODS: Thirty three transplant recipients with CMV illness (symptomatology with IgM and/or nPCR positive status), 20 recipients who were asymptomatic in the 6 months of follow up after transplantation and 62 healthy controls were investigated for markers of CMV infection. These individuals were tested for IgG avidity and neutralizing antibody by ELISA techniques. RESULTS: All 53 transplant recipients were found to have an IgG avidity index of > 50 per cent. Antibody to a CMV envelope glycoprotein gB/AD-1 (putative neutralizing antibody) was expressed as S/N ratio and was > or = 5 in asymptomatic (65%) and symptomatic (27%) immunosuppressed renal transplant recipients. However, none of the 53 CMV IgG positive healthy controls were positive for neutralizing antibodies S/N ratio > or = 5 (S/N ratio = sample mean OD/mean OD of 3 negative controls in each run). We observed the simultaneous presence of CMV PCR signal in leukocytes and neutralizing antibody (S/N ratio > or = 5) in the plasma in 22 (41.5%) of the 53 renal transplant recipients. INTERPRETATION & CONCLUSIONS: In this study among the immunosuppressed transplant patients we observed an association between symptomatic disease and the relative absence of neutralizing antibodies. The neutralizing antibodies are less frequently demonstrable among controls; while appearance in a higher proportion of asymptomatic recipients especially in association with high IgG avidity (> 90%) is suggestive of its role in control of CMV disease despite reactivation as evidenced by DNAemia while on immunosuppressive therapy.

Pre- and postrenal transplantation pharmacokinetics of cyclosporine microemulsion.

UNLABELLED: The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit. METHODS: We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC. RESULTS: The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations. CONCLUSIONS: CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.

Severe hyponatraemia: current concepts on pathogenesis and treatment.

Severe hyponatraemia (serum sodium <120 mEq/L) is a serious electrolyte disorder associated with life-threatening neurological complications. It develops most often when the ability of the kidney to excrete free water is impaired. The initial adaptation of the brain to hyponatraemia includes loss of water, sodium, potassium and chloride into the cerebrospinal fluid and the late adaptation consists of the loss of organic osmolytes. Adaptation of the brain to hyponatraemia causes potential problems during therapy, as re-adaptation requires a considerably longer time. Rapid correction of hyponatraemia may lead to the development of the osmotic demyelination syndrome. Though the ideal treatment for severe hyponatraemia remains controversial, a consensus regarding therapeutic guidelines has emerged. The rate of correction and the type of infusate depend on the duration and cause of the hyponatraemia, clinical presentation, volume status, renal function and the serum potassium level. The prognosis of the osmotic demyelination syndrome is rather dismal although several therapeutic modalities have been tried.