Anti-neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Secondary to Hydralazine: A Case Report.

Hydralazine is a vasodilator used in the treatment of resistant hypertension. It is a safe and widely used antihypertensive medicine. Its common adverse effects include headache, rebound tachycardia, fluid retention, and angina. It is a rare cause of anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with pulmonary and renal involvement. We report a case of a 74-year-old woman, with over eight years of use of hydralazine, who presented to the hospital with shortness of breath and cough. Blood work revealed deranged renal function with high creatinine levels. Serology workup was positive for anti-histone antibodies (AHA), anti-nuclear antibodies (ANA), myeloperoxidase (MPO) ANCA and proteinase-3 (PR-3) ANCA. Renal biopsy showed diffusely flattened tubular epithelium, focal micro vesicular degeneration, and focal loss of the brush border of the proximal tubular epithelium. Hydralazine was stopped and the patient was treated with corticosteroids, resulting in the resolution of her kidney injury.

Membranous Glomerulonephritis as an Uncommon Presentation of Secondary Syphilis: A Reminder on Therapeutic Decision-Making in Clinical Practice.

Membranous glomerulonephritis is one of the common causes of nephrotic syndrome in the adult population. It is idiopathic in the majority of patients, but the secondary forms can be seen in the setting of autoimmune disease, cancer, infection, and following exposure to certain medications. However, subclinical syphilis-related membranous nephropathy remains a particularly rare clinicopathologic entity in modern times. In this article, we chronicle an interesting case of latent syphilis masquerading as membranous glomerulonephritis, which resolved with benzathine penicillin without requiring immunosuppressive treatment. We further supplement this paper with a concise review of the relevant literature that delineates the utility of appropriate antibiotic therapy in the management of luetic membranous nephropathy. Clinicians should remain cognizant of secondary syphilis while evaluating patients for possible glomerulonephritis or those presenting with proteinuria. Additionally, patients with hepatitis B, hepatitis C, and human immunodeficiency virus infections are not infrequently coinfected with Treponema pallidum. Therefore, a high index of suspicion for systemic manifestations of syphilis such as nephrotic syndrome is warranted in the setting of a coinfection. Prompt diagnosis and treatment of syphilis may result in resolution of proteinuria, without the need for standard immunosuppressive therapy commonly used in clinical practice.

Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial.

BACKGROUND AND OBJECTIVES: Endothelial dysfunction is common among patients with CKD. We tested the efficacy and safety of combination treatment with sodium nitrite and isoquercetin on biomarkers of endothelial dysfunction in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This randomized, double-blind, placebo-controlled phase 2 pilot trial enrolled 70 patients with predialysis CKD. Thirty-five were randomly assigned to combination treatment with sodium nitrite (40 mg twice daily) and isoquercetin (225 mg once daily) for 12 weeks, and 35 were randomly assigned to placebo. The primary outcome was mean change in flow-mediated vasodilation over the 12-week intervention. Secondary and safety outcomes included biomarkers of endothelial dysfunction, inflammation, and oxidative stress as well as kidney function, methemoglobin, and adverse events. Intention-to-treat analysis was conducted. RESULTS: Baseline characteristics, including age, sex, race, cigarette smoking, history of hypertension and diabetes, use of renin-angiotensin system blockers, BP, fasting glucose, lipid profile, kidney function, urine albumin-creatinine ratio, and endothelial biomarkers, were comparable between groups. Over the 12-week intervention, flow-mediated vasodilation increased 1.1% (95% confidence interval, -0.1 to 2.3) in the treatment group and 0.3% (95% confidence interval, -0.9 to 1.5) in the placebo group, and net change was 0.8% (95% confidence interval, -0.9 to 2.5). In addition, changes in biomarkers of endothelial dysfunction (vascular adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, vWf, endostatin, and asymmetric dimethylarginine), inflammation (TNF-α, IL-6, C-reactive protein, IL-1 receptor antagonist, and monocyte chemoattractant protein-1), and oxidative stress (oxidized LDL and nitrotyrosines) were not significantly different between the two groups. Furthermore, changes in eGFR, urine albumin-creatinine ratio, methemoglobin, and adverse events were not significantly different between groups. CONCLUSIONS: This randomized phase 2 pilot trial suggests that combination treatment with sodium nitrite and isoquercetin did not significantly improve flow-mediated vasodilation or other endothelial function biomarkers but also did not increase adverse events compared with placebo among patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Nitrite, Isoquercetin, and Endothelial Dysfunction (NICE), NCT02552888.

Echocardiographic Evaluation of Left Atrial Volume Index in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) patients are at high risk of developing cardio vascular disease. Left atrial volume index (LAVi) is an indicator of left ventricular diastolic dysfunction. We conducted this study to find out the correlation of LAVi and other echocardio- graphic parameters with estimated glomerular filtration rate (eGFR). We prospectively enrolled 170 individuals: 69 patients with CKD and 101 controls. Echocardiographic parameters including systolic and diastolic volumes of left ventricle, LAVi, ejection fraction (EF), pulmonary artery systolic pressure (PASP), and E/e ratio were measured in all participants. The demographic, clinical, and echocardiographic parameters were examined. From the total of 170 individuals, 69 (40.5%) patients had CKD and 101 (59.5%) had normal renal profile. There were 38 (55.07%) males in the CKD group and 71 (70.29%) in the control group. Patients with CKD had higher median LAVi [33.33 mL/m2 ± 11.71 vs. 22.54 mL/m2 ± 5.82; P < 0.001], higher median E/e ratio [10.41 ± 6.28 vs. 7.48 ± 2.28; P < 0.001], higher median PASP [42.47 ± 13.64 vs. 33.59 ± 12.51; P < 0.001], and lower median EF [52.79% ± 14.37 vs. 60.7% ± 8; P < 0.001]. There was a statistically significant negative correlation of eGFR with LAVi (r = -0.515, P < 0.001), PASP (r = -0.44, P = 0.001), and E/e ratio (r = -0.331, P = 0.001). Patients with CKD have higher LAVi, PASP, and E/e ratio and lower EF as compared to individuals without CKD. There is a significant negative correlation between eGFR and LAVi.

Cocaine-Induced Acute Interstitial Nephritis: A Comparative Review of 7 Cases.

Acute interstitial nephritis is a well-known cause of acute kidney injury, but its association with cocaine use is extremely rare. In this article, we chronicle the case of a patient who developed acute interstitial nephritis secondary to cocaine insufflation. Furthermore, we conducted a systematic literature search of MEDLINE, Cochrane, Embase, and Scopus databases regarding cocaine-induced acute interstitial nephritis. A comprehensive review of the search results yielded a total of 7 case reports only. The data on patient characteristics, clinical features, biochemical profiles, treatment, and outcomes were collected and analyzed. This paper illustrates that acute interstitial nephritis may be added to the list of differentials in patients with acute kidney injury and a history of cocaine use. The therapeutic approach for cocaine-related kidney disease may be different than other etiologies responsible for acute renal insult. Prompt recognition of this entity is crucial because such patients may ultimately develop severe deterioration in renal function.

Primary renal lymphoma: a comprehensive review of the pathophysiology, clinical presentation, imaging features, management and prognosis.

Primary renal lymphoma (PRL) is defined as a non-Hodgkin's lymphoma restricted to kidneys with the absence of extensive nodal disease. It is an exceedingly rare clinicopathological entity, accounting for 0.7% of extranodal lymphomas. Published medical literature regarding the natural history and clinical outcomes of PRL remains limited. We describe a case of a young patient who presented with left shoulder pain, continuous fever, and unexplained weight loss as atypical initial manifestations of bilateral PRL, confirmed with the standard set of investigations. Furthermore, this article reviews the literature and discusses various aspects of PRL, including pathophysiology, presentation patterns, imaging and pathological characteristics, management, and prognosis. This paper serves to provide an update and aims to enhance the understanding of PRL. Timely diagnosis and treatment are imperative to achieve improved outcomes. Clinicians should maintain a high index of suspicion in order to prevent morbidity and mortality associated with this serious disease.

Treatment of cardiac nocardiosis in a post-renal transplant patient of systemic nocardiosis.

In general, nocardia infects immunosuppressed patients, however, sometimes it can also infect immunocompetent individuals. Nocardia infection can disseminate to any organ system of the body but the pulmonary system is the most commonly involved system. In some rare cases, the heart can also be involved and the resulting cardiac mycetoma can be treated successfully with antimicrobials without the need of surgery, unlike fungal cardiac mycetomas wherein surgery may be required in addition to antimicrobial therapy. We present an interesting case of post-renal transplant cardiac nocardiosis, which was treated successfully with a course of antibiotics.

Nicotinic Acid as a Phosphate-lowering Agent in Patients with End-stage Renal Disease on Maintenance Hemodialysis: A Single-center Prospective Study.

Background Hyperphosphatemia increases the risk of mortality and morbidity in patients with end-stage renal disease (ESRD). In addition to dietary restriction and renal replacement therapy, phosphorus-binding agents are the mainstay of treatment. While the use of calcium-containing binders has certain limitations, non-calcium-based binders are expensive and not readily available in developing countries. Previous studies on nicotinic acid as a phosphorus-lowering agent have limited data. In this study, we evaluated the efficacy of nicotinic acid in patients with ESRD on hemodialysis (HD) in Pakistan. Methods Forty-five patients with ESRD on maintenance HD having serum phosphorus levels >5.5 mg/dL were recruited. Nicotinic acid 250 mg was administered with food for four weeks. All patients with serum phosphorus levels <8 mg/dL were placed on a twice-daily regimen while the rest received it three times a day with meals. Patients were assessed at the beginning and end of the study with serum phosphorus levels. Results Mean age of the sample population was 44.6 ± 13.9 years and 57.8% of participants were male. Serum phosphorus level before treatment ranged from 5.6 to 10.8 mg/dL (mean, 6.91 ± 1.33). After nicotinic acid therapy, it ranged from 2.60 to 8.70 mg/dL (mean, 5.82 ± 1.40). Mean decrease in serum phosphorus levels with nicotinic acid after one month of treatment was 1.08 ± 1.16 mg/dL (p-value <0.001). Conclusion Nicotinic acid is effective in lowering serum phosphorus levels in patients with ESRD who are under renal replacement therapy with maintenance HD.

Clinical and Etiological Spectrum of Hypokalemic Periodic Paralysis in a Tertiary Care Hospital in Pakistan.

Introduction Hypokalemic periodic paralysis (HPP) is characterized by muscle weakness secondary to low serum potassium levels. It may be primary in origin or there may be secondary causes like thyrotoxic periodic paralysis, renal or suprarenal causes, or non-renal causes like gastroenteritis. Aim To study the etiology, clinical manifestations, and outcome after therapy of patients with hypokalemic paralysis. Methodology The study was conducted from January 2016 to December 2016. Patients fulfilling the diagnostic criteria for hypokalemic paralysis, i.e., flaccid muscle weakness involving two or more limb muscles due to serum potassium < 3.5 mmol/L and with no objective sensory signs were included in the study. Relevant investigations were done. Those with other causes of flaccid weakness or on diuretic therapy were excluded from the study. Data was analyzed using SPSS Version 20.0 (IBM Corp., Armonk, NY). Results In our study, 14 patients out of a total of 18 (14/18, i.e., 77.78%) were male and 4/18 (22.22%) were female [Male: Female ratio: 3.5:1]. The mean age of onset of HPP in males (29.5±10.14 yrs.) was lesser than that of females (41±10.8 yrs.), but this difference was statistically not significant (p<0.066). In the entire sample there were 15/18 cases (83.33%) of primary and 3/18 (16.67%) cases of secondary HPP [2/3 had thyrotoxic periodic paralysis and 1/3 had gastroenteritis]. Furthermore, 12/18 patients (66.66%) had symmetrical weakness (five cases of paraparesis and all were male; seven cases of quadriparesis: six males and one female) and 6/18 (33.33%) had asymmetrical weakness (two paraparesis: one male, one female; four quadriparesis: two males, two females). Statistically, no significant difference (p<0.709) was seen in those with symmetrical versus those with asymmetrical weakness. In this study 7/18 (38.89%) cases had absent, 1/18 (5.55%) had diminished, and 10/18 (55.55%) cases had intact deep tendon reflexes. None of the cases had cranial, bulbar, or respiratory involvement. The mean serum potassium of sample was 3.18±0.5 standard deviation (SD). The reduction in serum potassium was moderate (2.5-3.5 mmol/L) in primary and severe (<2.5 mmol/L) in secondary HPP. Those with quadriparesis had severe hypokalemia with a mean serum potassium of 2.1 mmol/L. Only 3/18 patients had concomitant magnesium deficiency. Patients given intravenous potassium replacement (except one with moderate hypokalemia and given oral replacement) recovered dramatically. The mean recovery time was 38.6±20.3 hours. The recovery time in quadriparesis was about 24 hours and in paraparesis was 12 hours. Only one patient with thyrotoxic periodic paralysis (TPP) and with severe serum potassium deficiency (0.9 meq/L) died due to cardiac arrhythmia. No atypical presentation was seen. Conclusion HPP has male preponderance. The age of onset of HPP is earlier in males than in females. Moreover, males are more prone to have symmetrical weakness. Asymmetrical weakness has almost an equal gender distribution. Primary hypokalemic paralysis is more frequent than secondary. Thyrotoxic periodic paralysis is the commonest cause of secondary periodic paralysis. The recovery time in quadriparesis is almost double the recovery time in paraparesis. Respiratory involvement is rare. HPP is an important differential in the diagnosis of acute flaccid muscle weakness. It should be promptly addressed to prevent recurrence of paralysis.

Characteristics and Outcome of Obstetric Acute Kidney Injury in Pakistan: A Single-center Prospective Observational Study.

Introduction Acute kidney injury (AKI) continues to be a cause of increased morbidity and mortality in pregnant women. While studies have been conducted on the incidence and etiology of this complication, the outcomes of obstetric AKI have not been extensively investigated. The primary focus of this prospective observational study was to analyze the risk factors, etiologies as well as maternal and fetal outcomes of AKI in pregnant females in Pakistan. Methods A total of 56 patients with obstetric AKI were recruited. Patients were followed for a period of three months postpartum. The diagnosis and staging of AKI were based on the classification of the Acute Kidney Injury Network (AKIN). Results Fifteen patients were lost to follow-up and were excluded from the study. The mean age of the remaining 41 patients was 26±6 years. Twenty-two (54%) patients were multigravida, and 19 (46%) were primigravida. Twenty (48%) patients did not receive any antenatal care, 13 (31%) were visited by a traditional birth attendant, and only eight (19%) had adequate antenatal care by a gynecologist. Out of 41 patients, seven (17%) presented before 28 weeks, and 34 (83%) patients presented after 28 weeks of gestation. Four (10%) patients were found to be in stage I, four (10%) in stage II, and 33 (80%) patients in stage III AKI during hospitalization. The causes of AKI included sepsis in 32 (78%), intrauterine death in 24 (60%), postpartum hemorrhage in 17 (41%), shock in 15 (36%), pre-eclampsia/eclampsia in seven (17%), and coagulopathy in three (7%) patients. Twenty-eight (68.3%) patients received hemodialysis during the hospital stay. Three-month follow-up showed complete resolution of AKI in 14 (34.2%) patients, partial resolution in seven (17%), end-stage renal disease in 10 (24.4%), and death in 10 (24.4%) patients. Conclusion The present study indicates that a vast majority of patients with obstetric AKI require dialysis. Residual renal dysfunction and end-stage renal disease were common at the three-month follow-up. Incidentally, sepsis and intrauterine death were the leading causes in this study population. Increased awareness and appropriate obstetrical care may have a significantly positive impact on decreasing the morbidity and mortality in these patients.

Cardiovascular Autonomic Neuropathy and its Association with Cardiovascular and All-cause Mortality in Patients with End-stage Renal Disease.

Background End-stage renal disease frequently leads to increased cardiovascular mortality. Cardiovascular autonomic neuropathy (CAN) may be predictive of cardiac arrhythmias and sudden cardiac death in patients with end-stage renal disease. Methods A total of 70 patients with end-stage renal disease were included in the study. The assessment of cardiac dysautonomia was based on the four standardized tests performed at the baseline and, again, at the end of the study. The criteria for CAN included at least two abnormal test results. Results Fifty of 70 patients completed the study and were followed-up after one year. Out of the 50 patients, 44 (88%) had CAN at baseline. Twelve (24%) patients died at the one-year follow-up. Sudden cardiac death was reported in seven out of 12 (58%) patients. All seven patients who died had high dysautonomia scores (three abnormal tests) at the baseline. There was a significantly higher percentage of patients with all four abnormal tests amongst patients who died of any cause (56% vs. 17%; RR 6.07, 95% CI 1.29-28.49; p-value 0.02) or due to sudden cardiac death (43% vs. 10.5%; RR 6.37, 95% CI 1.03-39.36; p-value 0.04). All five patients who did not have CAN at the baseline developed this abnormality on repeat testing after one year. Conclusion The prevalence of CAN in patients with end-stage renal disease on maintenance hemodialysis was significantly higher. CAN was an independent predictor of all-cause and cardiovascular mortality, which highlights it as a risk stratification tool in patients with end-stage renal disease.

Van der Knaap Disease.

Van der Knaap disease or megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare, inherited, autosomal recessive disorder. It is characterised by macrocephaly and slowly progressive ataxia, spasticity, and cognitive decline. The usual age of onset is described from birth to infancy. MLC predominantly occurs in some ethnicities where consanguinity is common. This disease is caused by mutations in the gene, which encodes a novel protein, MLC1. The characteristic MRI findings include leukodystrophy and subcortical cysts that yield diagnostic clue in most of the cases. The diagnosis can be established prenatally and genetic counseling is usually offered for future pregnancies. Herein, we chronicle a case of Van der Knaap disease from Pakistan with the classical MRI features.

Brucellosis in renal transplant recipients: a comparative review of 5 cases.

Although brucellosis in renal transplant recipients is rare, we studied the clinical characteristics of this infection in this patient population due to the significantly increased number of renal transplantations performed over the past few decades. We report one case from our experience and undertake a review of the previously reported cases retrieved from the PubMed. A total of 5 cases of brucellosis in renal transplant recipients were found to date. The mean time from transplantation to diagnosis of brucellosis was 4.7 years (range, 4 months to 13 years). Blood culture and detection of anti-Brucella antibodies were frequently used diagnostic investigations. Treatment with appropriate antibiotic regimen led to a clinical cure and marked improvement in Brucella titre in all the patients. This review illustrates that clinicians should remain vigilant for this infectious aetiology following renal transplantation. Further studies are required to delineate the magnitude and scope of this association.

The Syndrome of Diabetic Amyotrophy: A Preventable Disaster?

Diabetic amyotrophy is a disabling syndrome that frequently has a difficult or delayed clinical recognition. It is characterised by lancinating pain followed by muscle weakness, usually in the hip and thigh. The disease predominantly occurs in elderly patients and causes significant morbidity. Although a detailed history and neurologic examinations are helpful, electrodiagnostic testing yields accurate diagnosis in most of the cases. Herein, we chronicle the case of a young patient who developed profound diabetic amyotrophy within five years after the onset of type 1 diabetes mellitus. Furthermore, this report highlights the preventive as well as therapeutic role of strict glycemic control, warranting population-based monitoring and education of patients for diabetic amyotrophy, especially in Pakistan.

Fatal Hypermagnesemia Due to Laxative Use.

We report a case of fatal hypermagnesemia in a 53-year-old woman admitted for acute exacerbation of chronic obstructive pulmonary disease and with a history of chronic constipation treated regularly with magnesium-containing laxatives. On admission, her magnesium level was 2.0mg/dL, which rose to a peak of 10.8mg/dL despite hydration and diuresis in the presence of a normal kidney function. Continuous renal replacement therapy was promptly initiated, which reduced her serum magnesium levels, but her condition continued to deteriorate precipitously progressing to shock leading to oligoanuric renal failure, and she died 2 days later. A review of the literature shows that though rare and often unsuspected, severe hypermagnesemia frequently results in death even in individuals with normal renal function despite renal replacement therapy. In patients with constipation, retention of magnesium-based laxative in the gut apparently serves as a reservoir for continuous magnesium absorption and contributes to mortality.

The development of malnutrition is not dependent on its traditional contributing factors in patients on maintenance hemodialysis in developing countries.

Malnutrition in dialysis population is associated with significant morbidity and mortality. Nutritional assessment is a neglected area in hemodialysis (HD) patients in developing countries. The aim of the study was to find out whether any traditional parameters have statistically significant correlation with malnutrition. All 58 end-stage renal disease patients on maintenance HD in our dialysis unit were enrolled in this cross-sectional study. The nutritional status was assessed by a predesigned questionnaire including subjective global assessment (SGA). Anthropometric measurements, peripheral neuropathy, and pertinent laboratory parameters were checked. The duration of HD ranged between three months to 10 years (mean 4 ± 1.5 years). Of these 49 patients, 26 (53%) were males with a median age 45 (25-76) years. Fifteen patients (31%) were well nourished and 34 (69%) were undernourished including nine (19%) patients classified as severely malnourished according to SGA. Malnutrition appeared more prevalent in males, however, statistically not significant (P = 0.063). On univariate and multivariate analysis, no significance was found across well-nourished and malnourished patients in terms of age, body mass index, calorie count, duration and frequency of dialysis, dry weight, interdialytic weight loss or gain in the past six months, body fat percentage, serum albumin, blood pressure, intradialytic hypotension, urea reduction ration, Kt/Vurea, peripheral neuropathy, and comorbidities. Psychosocial factors were identified in 24 (49%) patients with 19 (79%) having some degrees of malnutrition, but the finding did not reach the statistical significance. Surprisingly, the traditional factors studied in previous trials have not shown any significant association to malnutrition in our study based on the statistical analysis.

Managing Postural Hypotension in Diabetic Autonomic Dysfunction When Adrenergic Drugs are Contraindicated: Case Report and Review of Literature.

Postural hypotension, as a manifestation of autonomic neuropathy is a very sinister long-term debilitating complication of diabetes, is usually irreversible and tough to manage with medications. The treatment of this condition following the standard treatment protocols can be contraindicated in the patients with underlying heart conditions. We report the case of a patient at our hospital who presented with full-blown symptomatic dysautonomia secondary to long-standing diabetes, with bedside testing positive for autonomic dysfunction. Treating this patient with the standard protocol of adrenergic agonist could have worsened his underlying coronary artery disease. So, we moved a step aside to go out of the box and we have a trial of the ß1-selective beta-blocker, with astonishing results and significant improvement in the quality of life and symptoms of postural hypotension. We report here the use of alternative treatment option in managing a patient with severe postural hypotension secondary to diabetes-related autonomic neuropathy when adrenergic drugs are contraindicated.