Early Ultrastructural Changes in Biopsies From Patients With Symptomatic CKD of Uncertain Etiology.

Introduction: Although the investigation of chronic kidney disease of uncertain etiology (CKDu) has identified many possible influencing factors in recent years, the exact pathomechanism of this disease remains unclear. Methods: In this study, we collected 13 renal biopsies from patients with symptomatic CKDu (Sym-CKDu) from Sri Lanka with well-documented clinical and socioeconomic factors. We performed light microscopy and electron microscopic evaluation for ultrastructural analysis, which was compared with 100 biopsies from German patients with 20 different kidney diseases. Results: Of the 13 Sri Lankan patients, 12 were men (92.3%), frequently employed in agriculture (50%), and experienced symptoms such as feeling feverish (83.3%), dysuria (83.3%), and arthralgia (66.6%). Light microscopic evaluation using activity and chronicity score revealed that cases represented early stages of CKDu except for 2 biopsies, which showed additional signs of diabetes. Most glomeruli showed only mild changes, such as podocyte foot process effacement on electron microscopy. We found a spectrum of early tubulointerstitial changes including partial loss of brush border in proximal tubules, detachment of tubular cells, enlarged vacuoles, and mitochondrial swelling associated with loss of cristae and dysmorphic lysosomes with electron-dense aggregates. None of these changes occurred exclusively in Sym-CKDu; however, they were significantly more frequent in these cases than in the control cohort. Conclusion: In conclusion, our findings confirm the predominant and early alterations of tubular structure in CKDu that can occur without significant glomerular changes. The ultrastructural changes do not provide concrete evidence of the cause of CKDu but were significantly more frequent in Sym-CKDu than in the controls.

Atypical hemolytic uremic syndrome: a case report.

BACKGROUND: Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any organ of the body leading to thrombocytopenia, Coombs-negative hemolytic anemia, and end-organ damage. The most common forms of thrombotic microangiopathies are Shiga toxin-producing Escherichia coli-mediated hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome. The atypical hemolytic uremic syndrome occurs due to genetic and acquired mutations in complement regulatory factors and to complement activation factors in the immune system, mainly the alternative pathway. Clinical manifestations and outcomes differ with the prevalent mutations of the patient. Currently, available treatment modalities are therapeutic plasma exchange and a monoclonal antibody against C5, eculizumab. We report a case of a Sri Lankan girl diagnosed with atypical hemolytic uremic syndrome complicated with septicemia, hemolytic anemia, acute kidney injury, pulmonary hemorrhage with respiratory failure, and hypertension who had a complete remission following long-term (30 months) therapeutic plasma exchange. CASE PRESENTATION: A 15-year-old Sri Lankan girl was transferred from a local hospital with the features of septicemia and acute kidney injury for specialized management. She had high blood pressure (180/100 mmHg) on admission. She underwent appendicectomy based on suspicion of acute appendicitis as the cause of sepsis. Following surgery, her condition deteriorated, and intensive care unit management was warranted because she developed pulmonary hemorrhages and respiratory failure requiring mechanical ventilation and renal replacement therapy in the form of hemodialysis. Her blood investigations showed microangiopathic hemolytic anemia, thrombocytopenia, elevated lactate dehydrogenase, and reduced human complement C3 levels, together with a normal coagulation profile. She was diagnosed with atypical hemolytic uremic syndrome and was initiated on therapeutic plasma exchange and other supportive therapy, including corticosteroids. Following a lengthy course of plasma exchange, complete recovery was achieved. CONCLUSION: The atypical hemolytic uremic syndrome is a rare disease entity requiring a high index of suspicion to diagnose. It is a diagnosis of exclusion. Early diagnosis with prompt treatment will render a better outcome. The atypical hemolytic uremic syndrome needs to be considered in all patients with thrombotic microangiopathy.

Ethylene glycol intoxication following brake fluid ingestion complicated with unilateral facial nerve palsy: a case report.

BACKGROUND: Brake oil is an automobile transmission fluid composed of a mixture of toxic alcohols such as ethylene glycols and glycol ethers. Both accidental and intentional ingestion cases have been reported and they can present with multisystem involvement. Life-threatening complications evolve from deleterious effects on cardiopulmonary and renal systems. Effects on neurological and gastrointestinal systems give rise to a multitude of complications although non-fatal in nature. The biochemical panel consists of a high concentration of ethylene glycol with severe metabolic acidosis, high anion gap, high osmolar gap, oxaluria, and hypocalcemia. The mainstay of treatment is enhanced elimination of ethylene glycol and its metabolites by hemodialysis, together with general supportive care, gastric decontamination, and vitamins such as thiamine and pyridoxine to minimize the adverse effects of intoxication. CASE PRESENTATION: A 26-year-old Sinhalese woman presented with reduced urine output, shortness of breath, reduced level of consciousness, abdominal pain, and vomiting with mild degree fever of 2 days' duration. She had bilateral lower limb edema, crepitations over bilateral lower lung fields, and right-sided lower motor type facial nerve palsy. Investigations showed severe metabolic acidosis with high anion gap and high osmolar gap. With regular hemodialysis she made a complete recovery after 3 months. CONCLUSION: Even without a clear history of poisoning, the presence of a high anion, high osmolar gap metabolic acidosis should prompt one to search for ethylene glycol ingestion. Uncommon manifestations like cranial neuropathies need to be examined and considered. Timely aggressive treatment leads to a better prognosis.

Multicentric Castleman disease of hyaline vascular variant presenting with unusual systemic manifestations: a case report.

BACKGROUND: Castleman disease is a rare lymphoproliferative disorder presenting with localized or disseminated lymphadenopathy and systemic manifestations. It can be categorized in numerous ways, such as unicentric versus multicentric, histopathological variants (hyaline-vascular, plasma cell, and mixed), or subtypes based on causative viral infections (human immunodeficiency virus, human herpesvirus-8, or Kaposi sarcoma herpesvirus). Presentation ranges from asymptomatic to symptoms involving multiple organs. Even though the exact mechanism of pathogenesis is unknown, treatment is directed toward possible etiologies such as interleukin-6, cluster of differentiation 20, and viral agents. CASE PRESENTATION: A 36-year-old Sri Lankan woman presented with generalized body swelling and foamy urine of 2 weeks' duration. Examination revealed pallor; generalized edema; axillary, cervical, and inguinal lymphadenopathy; hypertension; and hepatomegaly. Investigations showed bicytopenia, nephrotic range proteinuria with hypoalbuminemia, hypogammaglobulinemia, and features of hyaline-vascular type Castleman disease in a lymph node biopsy. She was managed with rituximab and had good clinical improvement. CONCLUSIONS: Castleman disease has a broad spectrum of clinical manifestations, disease pathogeneses, and associations and/or complications. Medical professionals need to be familiar with this spectrum because timely diagnosis and aggressive targeted therapy are the cornerstones of managing these patients.

Star fruit toxicity: a cause of both acute kidney injury and chronic kidney disease: a report of two cases.

BACKGROUND: Star fruit (Averrhoa carambola) is commonly consumed as a herbal remedy for various ailments in tropical countries. However, the dangers associated with consumption of star fruit are not commonly known. Although star fruit induced oxalate nephrotoxicity in those with existing renal impairment is well documented, reports on its effect on those with normal renal function are infrequent. We report two unique clinical presentation patterns of star fruit nephrotoxicity following consumption of the fruit as a remedy for diabetes mellitus-the first, in a patient with normal renal function and the second case which we believe is the first reported case of chronic kidney disease (CKD) due to prolonged and excessive consumption of star fruits. CASE PRESENTATION: The first patient is a 56-year-old female diabetic patient who had normal renal function prior to developing acute kidney injury (AKI) after consuming large amount of star fruit juice at once. The second patient, a 60-year-old male, also diabetic presented with acute on chronic renal failure following ingestion of a significant number of star fruits in a short duration with a background history of regular star fruit consumption over the past 2-3 years. Both had histologically confirmed oxalate induced renal injury. The former had histological features of acute tubulo-interstitial disease whilst the latter had acute-on-chronic interstitial disease; neither had histological evidence of diabetic nephropathy. Both recovered over 2 weeks without the need for haemodialysis. CONCLUSION: These cases illustrate the importance of obtaining the patient's detailed history with respect to ingestion of herbs, traditional medication and health foods such as star fruits especially in AKI or CKD of unknown cause.

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages.

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.

Retrospective analysis of renal histology in asymptomatic patients with probable chronic kidney disease of unknown aetiology in Sri Lanka.

OBJECTIVES: To study the early pathological changes in renal lesions of asymptomatic patients with kidney diseases, with no definite aetiology living in regions endemic for chronic kidney disease of unknown etiology (CKDUe). Design Retrospective study. SETTING: Regions endemic for CKDUe in and around the North Central Province of Sri Lanka. STUDY POPULATION: Two hundred and eleven asymptomatic patients living in endemic regions detected with renal disease by screening for proteinuria using the dipstick method. Those with long standing hypertension, diabetes mellitus, histological diagnosis of primary glomerular diseases, immunocomplex mediated diseases or renal lesions secondary to systemic diseases were excluded. MEASUREMENTS: Renal lesions were divided into seven histological categories depending on the pathological changes: Category 0: no detectable changes. Category 1: Interstitial fibrosis ± mild interstitial inflammation ± tubular atrophy; no glomerulosclerosis. Category 2: Interstitial fibrosis ± mild interstitial inflammation ± tubular atrophy; glomerulosclerosis. Category 3: Moderate or severe interstitial fibrosis, interstitial inflammation and tubular atrophy ± glomerulosclerosis; Category 4: Interstitial inflammation ± tubular atrophy ± glomerulosclerosis; no interstitial fibrosis. Category 5: The prominent change is interstitial inflammation with tubulitis. Category 6: Severely scarred kidney. Histological categories were compared with calculated glomerular filtration rates and age of the patients. RESULTS: Number of cases in histological categories 0 to 6 were: 7 (3.3%), 71 (33.6%), 53 (25.1%), 63 (29.9%), 0, 2 (0.9%) and 15 (7.1%) respectively. The mean glomerular filtration rate was >90 ml/min in patients in category 0 and 1 and declined progressively in categories 2 and 3. Apart from category 0, all had interstitial fibrosis and in category 1, 62 (87.3%) had interstitial fibrosis without inflammation. Severity of interstitial inflammation increased from category 1 to 3. CONCLUSIONS: The early disease among asymptomatic patients is characterized by interstitial fibrosis without significant interstitial inflammation and glomerular sclerosis with preserved glomerular function. Although the role of interstitial inflammation in the initiation of the disease is not clear, it appears to have a role in the progression of the disease.

Chronic kidney disease in snake envenomed patients with acute kidney injury in Sri Lanka: a descriptive study.

BACKGROUND: Data on the long-term outcomes of acute kidney injury (AKI) in envenomed patients leading to chronic kidney disease (CKD) are scarce. The aim of the study was to investigate this issue and to determine the predictive factors in developing CKD. METHODS: The records of a series of 54 patients who had AKI following a snakebite during the period 2004-2009 and who had been followed up were reviewed in the nephrology unit, Kandy, Sri Lanka. The primary outcome measure was the failure of renal functions to return to normal within 1 year. The renal histology was studied in seven patients. RESULTS: The mean age of the group was 50 years (SD 13 years) and 39 (72%) patients were men. The offending snakes were Russell's viper and hump-nosed viper in 15 (28%) and 13 (24%) patients, respectively. At 1 year, 20 patients (37%) had developed CKD (CKD group) and the rest (63%) had recovered (recovered group). The acute stage serum creatinine was high in both groups with no difference (on admission, p=0.134; on discharge, p=0.323), but the CKD group showed significantly high serum creatinine at 2 months after AKI (p=0.004). Mean duration of renal replacement therapy (RRT) of the recovered group and CKD group were 7 (SD 5) and 16 (SD 12) days, respectively (p=0.015). Renal histology of six CKD patients showed predominant glomerular sclerosis and interstitial nephritis. CONCLUSIONS: CKD is an outcome of severe AKI following snake envenoming probably predicted by the length of RRT.