Suceena Alexander

Posterior reversible encephalopathy syndrome in a renal allograft recipient: A complication of immunosuppression?

Posterior reversible encephalopathy syndrome (PRES) is an uncommon post-renal transplant complication. We report a 16-year-old boy who had an acute cellular rejection immediate post-transplant and was given intravenous methylprednisolone along with an increase in tacrolimus dose. He was diagnosed to have PRES based on clinical and radiological features within 6 h of intensified immunosuppression. This is an unusual case report of successfully managing PRES with continuation of the intensified immunosuppression as warranted by the clinical situation, along with aggressive blood pressure control. After 6 weeks, magnetic resonance imaging showed complete resolution of lesions. He has good graft function and no residual neurological deficits while on small doses of three antihypertensives, 12 months after transplantation.

Effect of double filtration plasmapheresis on various plasma components and patient safety: A prospective observational cohort study

Double filtration plasmapheresis (DFPP) was historically used for blood group incompatible renal transplantation. Very few studies are available worldwide regarding its efficiency in removing specific plasma components, and safety. We conducted a prospective observational cohort study over 1 year on patients undergoing DFPP for various renal indications. There were 15 patients with 39 sessions. The pre- and post-procedure plasma samples of serum IgG, IgA, IgM, fibrinogen, calcium, phosphate, potassium, and magnesium were analyzed. The effluent albumin concentration was also measured, and complications during the hospital stay were recorded. Cumulative removal of serum IgG, IgA, IgM, fibrinogen, and albumin at the end of four sessions were 72%, 89%, 96%, 88.5%, and 21.3%, respectively and effluent albumin concentration was 1.75 – 2.0 times (range: 6.3 g/dl – 7.2 g/dl; mean ± standard deviation (SD) – 7 g/dl ± 0.3 g/dl) the preprocedural serum albumin (mean ± SD – 3.5 g/dl ± 0.5 g/dl). Removal of other plasma components were not statistically significant. Hypotensive episodes were observed only 16.6%, with the usage of effluent concentration albumin as replacement fluid despite an average 2.4 (mean ± SD – 2.4 ± 0.4 l) liters of plasma volume processing each session. DFPP removes IgG, IgA, IgM, fibrinogen, and albumin. The cumulative removal IgG (72%) is suboptimal, whereas IgA (89%) and IgM (96%) are comparable to historical controls. We observed lesser episodes (12.5%) of hypotension with effluent albumin concentration as replacement fluid, and all bleeding complications were observed when serum fibrinogen level was <50 mg/dl.

Profile of incident chronic kidney disease related-mineral bone disorders in chronic kidney disease Stage 4 and 5: A hospital based cross-sectional survey.

Chronic kidney disease related-mineral bone disorder (CKD-MBD) has been poorly studied in pre-dialysis Indian CKD patients. We aimed to study the clinical, biochemical and extra skeletal manifestations of untreated CKD-MBD in pre-dialysis Stage 4 and 5 CKD patients attending nephrology out-patient clinic at a tertiary care hospital in South India. A hospital based cross-sectional survey including, demographic profile, history of CKD-MBD symptoms, measurement of serum calcium, phosphate, parathyroid hormone, 25 hydroxy vitamin D (25(OH) D) and alkaline phosphatase; lateral abdominal X-rays for abdominal aortic calcification (AAC) and echocardiography for valvular calcification (VC) was carried out. Of the 710 patients surveyed, 45% had no CKD-MBD related symptom. Prevalence of hypocalcemia, hyperphosphatemia, hyperparathyroidism (>150 pg/mL) and 25(OH) D levels <30 ng/mL was 66.3%, 59%, 89.3% and 74.7% respectively. Echocardiography was carried out in 471 patients; 96% of whom had VC (calcification score ≥1). Patients with VC were older and had lower 25(OH) D levels than those without. Lateral abdominal X-rays were obtained in 558 patients, 6.8% of whom were found to have AAC, which was associated with older age. Indian patients with incident CKD-MBD have a high prevalence of hypocalcemia, 25(OH) D deficiency and VC even prior to initiating dialysis while AAC does not appear to be common. The association between 25(OH) D deficiency and VC needs further exploration.

Prospective blood pressure measurement in renal transplant recipients

Blood pressure (BP) control at home is difficult when managed only with office blood pressure monitoring (OBPM). In this prospective study, the reliability of BP measurements in renal transplant patients with OBPM and home blood pressure monitoring (HBPM) was compared with ambulatory blood pressure monitoring (ABPM) as the gold standard. Adult patients who had living-related renal transplantation from March 2007 to February 2008 had BP measured by two methods; OBPM and ABPM at pretransplantation, 2nd, 4th, 6th, and 9th months and all the three methods: OBPM, ABPM, and HBPM at 6 months after transplantation. A total of 49 patients, age 35 ± 11 years, on prednisolone, tacrolimus, and mycophenolate were evaluated. A total of 39 were males (79.6%). Systolic BP (SBP) and diastolic BP (DBP) measured by OBPM were higher than HBPM when compared with ABPM. When assessed using OBPM and awake ABPM, both SBP and DBP were significantly overestimated by OBPM with mean difference of 3-12 mm Hg by office SBP and 6-8 mm Hg for office DBP. When HBPM was compared with mean ABPM at 6 months both the SBP and DBP were overestimated by and 7 mm Hg respectively. At 6 months post transplantation, when compared with ABPM, OBPM was more specific than HBPM in diagnosing hypertension (98% specificity, Kappa: 0.88 vs. 89% specificity, Kappa: 0.71). HBPM was superior to OBPM in identifying patients achieving goal BP (89% specificity, Kappa: 0.71 vs. 50% specificity Kappa: 0.54). In the absence of a gold standard for comparison the latent class model analysis still showed that ABPM was the best tool for diagnosing hypertension and monitoring patients reaching targeted control. OBPM remains an important tool for the diagnosis and management of hypertension in renal transplant recipients. HBPM and ABPM could be used to achieve BP control.

Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two South Indian families with primary hyperoxaluria type 1 causing later onset end-stage kidney disease

Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase deficiency. Here, we describe two unrelated patients who were diagnosed to have primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation was detected in both the patients and the parents were found to be heterozygous carriers. Our patients developed end-stage renal disease at 23 years and 35 years of age. However, in the largest series published from OxalEurope cohort, the median age of end-stage renal disease for null mutations carriers was 9.9 years, which is much earlier than our cases. Our patients had slower progressions as compared to three unrelated patients from North India and Pakistan, who had homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further, patients need to be studied to find out if c.445_452delGTGCTGCT mutation represents a founder mutation in Southern India.

First case on successful management of manganism with renal transplantation.

With Renal Transplantation Manganese (Mn) has recently been detected in patients undergoing maintenance hemodialysis with deposition in the brain causing a clinical syndrome with parkinsonian features (1). We present a patient with end-stage renal disease on maintenance dialysis and manganism successfully managed with renal transplantation. This is, to our knowledge, the first case reporting the complete clinical and radiologic resolution of manganism with renal transplantation. A 49-year-old housewife with endstage renal disease secondary to diabetes was referred for renal transplantation while on irregular hemodialysis for approximately 1 year elsewhere. She presented to us with uremic features and chronic headache. There was no history suggestive of vasculitis, connective tissue disorders, indigenous medication use, well water consumption, or addictions. There was no exposure to industrial toxins or wastes and stainless steel utensils were used at home for cooking. The headache was bifrontotemporal, sharp, continuous, and severe enough to interfere with daily activities as well as to wake her up from sleep. There was no associated aura, photophobia, phonophobia, or vomiting and improved marginally with analgesic use. She did not give any history of giddiness or hearing impairment. She had features of depression, reduced social interaction, and conversation. Her blood pressure was well controlled. On examination, her blood pressure was 110/70 mm Hg. She had mask-like facies, bradykinesia, and slow speech. Signs suggestive of distal symmetrical sensory polyneuropathy involving both small and large fibers were elicited. Proliferative diabetic retinal changes without features of chronic hypertension or papilledema were observed on fundoscopy. She was evaluated for the chronic headache with magnetic resonance imaging (MRI) of the brain, which revealed symmetrical hyperintensity in the globus pallidii on T1-weighted sequences (Fig. 1A). The T2-weighted MR images were normal. These features were consistent with Mn deposition. Blood Mn level was 48.70Kg/L (normal, 6.70Y10.40Kg/L). She had anemia with iron overload (hemoglobin 9.1 g/dL [91 g/L], MCV 94 fl, transferrin saturation 51.3%, and ferritin 1455.7 ng/mL [1455.7 Kg/L]) and normal liver function tests. She was maintained on thrice a week hemodialysis thereafter until she underwent renal transplantation 6 months later. She was not started on any antiparkinsonism drugs. Many of her neurologic features, especially cognitive abnormalities and neuropathy, improved after renal transplantation. MRI of the brain done 15 months after renal transplantation showed normal appearance of the globus pallidii (Fig. 1B) with complete resolution of the clinical symptoms and the bilateral hyperintensities that were seen in the pretransplantation MRI study of the brain. She is doing well with normal allograft function on last follow-up 15 months after transplantation with blood Mn level of 10.45 Kg/L (normal, 6.70Y10.40 Kg/L). Once absorbed, Mn either complexes as Mn 3+ with transferrin or albumin or exists as Mn free ions. Glial cells have a capacity to concentrate Mn up to 200 times the extracellular concentration and the basal ganglia have abundant transferrin receptors, resulting in increased deposition of Mn. This leads to neuronal injury and gliosis resulting in dopaminergic dysfunction. This process seems accentuated in patients on hemodialysis. Urinary excretion of Mn is only 0.1% to 2%. Thus, anuric chronic kidney disease patients do not routinely manifest with high Mn levels (1). Symmetrical high signals in T1weighted images have also been noted in deposition of other paramagnetic substances such as iron in neurodegeneration with brain iron accumulation and calcium (previous radiation/chemotherapy, hyperparathyroidism, and Fahr’s disease), methemoglobin (hemorrhage), melanin, and as atypical MRI features of Wilson’s disease. The combination of clinical details and imaging helps to identify the underlying cause as in this case. Our patient did not receive any parenteral nutrition and had normal liver function tests and normal serum calcium. Unremarkable T2-weighted images and high serum ferritin level excludes neurodegeneration with brain iron accumulation and Wilson’s disease does not improve with dialysis or renal transplantation. The clinical scenario, symmetric MRI appearance, normal signal in T2-weighted images makes hemorrhage unlikely. Differentiation from Parkinson’s disease that is asymmetrical, has resting tremors and festinant gait, and responds to L-DOPA is important (2, 3). Our patient had high blood levels of Mn without any obvious exposure. Health supplements in hemodialysis patient (Chlorella extract) have been reported previously to cause manganism (4), but no such intake was disclosed. The absence of details regarding water source and treatment while on hemodialysis for nearly a year before presentation led us to consider Mn transfer during hemodialysis, possibly as a result of water contamination, especially in the absence of excessive Mn intake in diet or as supplements (2). Treatment options for Mn toxicity are limited.

Percutaneous PD catheter insertion after past abdominal surgeries

Sir, The preferred method of initiating renal replacement therapy in developing countries is probably the percutaneous peritoneal dialysis (PD) catheter insertion technique.[1] However, this is seldom practiced in those with a history of previous abdominal surgery,[2] where laparoscopy is preferred, as adhesiolysis can be done if needed.[2] From Christian Medical College, Vellore, we report our experience of successful percutaneous PD catheter insertion in 12 patients who had previous abdominal surgeries.

Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI— Glomerular Research And Clinical Experiments- Ig A Nephropathy in Indians—cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.

Spectrum of biopsy proven renal disease in South Asian children: Two decades at a tropical tertiary care centre

We report findings from a large single centre paediatric renal biopsy cohort in South Asia.

Hydroxycloroquine blood concentration in lupus nephritis: a determinant of disease outcome?

Background Hydroxychloroquine (HCQ) is a recommended drug in systemic lupus erythematosus (SLE). It has a long terminal half-life, making it an attractive target for therapeutic drug monitoring. The aim of this study was to establish a relationship between blood HCQ concentration and lupus nephritis activity. Methods We conducted a retrospective observational study with data collected from clinical and laboratory records. Inclusion criteria were patients followed in the lupus clinic with biopsy-proven International Society of Nephrology/Renal Pathology Society Classes III, IV or V lupus nephritis on HCQ for at least 3 months (200-400 mg daily) and with HCQ levels measured during treatment. Exclusion criteria were patients on renal replacement therapy at baseline or patients lost to follow-up. Results In 171 patients, the HCQ level was measured in 1282 samples. The mean HCQ blood level was 0.75±0.54mg/L and it was bimodally distributed. An HCQ level <0.20 mg/L [232 samples (18.1%)] appeared to define a distinct group of abnormally low HCQ levels. For patients in complete or partial remission at baseline compared with those remaining in remission, patients with renal flare during follow-up had a significantly lower average HCQ level (0.59 versus 0.81 mg/L; P= 0.005). Our data suggest an HCQ target level to reduce the likelihood of renal flares >0.6 mg/L (600 ng/mL) in those patients with lupus nephritis. Conclusion HCQ level monitoring may offer a new approach to identify non-adherent patients and support them appropriately. We propose an HCQ minimum target level of at least 0.6 mg/L to reduce the renal flare rate, but this will require a prospective study for validation.