| Abstract|| |
Diabetes and hypertension are at present the major causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. The stages 0–5 of CKD are defined according to the estimated glomerular filtration rate. The term chronic renal failure (CRF) typically corresponds to CKD stages 3–5. Cardiovascular disease is the main cause of morbidity and mortality in patients of CRF and ESRD. This study was undertaken to analyze the age and sex incidence, clinical features, etiology, pathology of various organs in detail, and causes of death of CRF patients. All autopsies performed on known cases of CRF and those who were diagnosed as CRF at autopsy at a tertiary care hospital in India over a 7-year period were studied. The highest number of cases of CRF fell within the 56–65 years age group with a male/female ratio of 1.38:1. Oliguria and anasarca were the most common presenting features. Chronic pyelonephritis was the most common cause of CRF in our study, followed by hypertension, diabetes, and chronic glomerulonephritis. Other causes included amyloidosis, autosomal poly- cystic kidney disease, and ischemic and multiple myeloma. Most common cause of death found was cardiovascular, followed by infections, cerebrovascular, metabolic, and other causes.
|How to cite this article:|
Padmanabhan A, Gohil S, Gadgil N M, Sachdeva P. Chronic renal failure: An autopsy study. Saudi J Kidney Dis Transpl 2017;28:545-51
|How to cite this URL:|
Padmanabhan A, Gohil S, Gadgil N M, Sachdeva P. Chronic renal failure: An autopsy study. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2019 Jul 18];28:545-51. Available from: http://www.sjkdt.org/text.asp?2017/28/3/545/206441
| Introduction|| |
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic pro cesses associated with abnormal kidney func tion and a progressive decline in glomerular filtration rate (GFR). The stages 0–5 of CKD are defined according to the estimated GFR.
The term chronic renal failure (CRF) typically corresponds to CKD stages 3–5. End-stage renal disease (ESRD) represents the final stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys results in the uremic syndrome.,
Diabetes and hypertension (HT) are at pre sent the major causes of ESRD worldwide. Cardiovascular disease is the main cause of morbidity and mortality in patients of CRF and ESRD. Analysis of cause of death in CRF provides information useful for counseling pa tients, targeting therapy, and directing future research efforts with the ultimate goal of reducing mortality and morbidity in CRF.
| Aims and Objectives|| |
Extensive search of literature revealed that not many autopsy studies, especially Indian studies, have been done on CRF. This autopsy study is undertaken to analyze the clinical features, age and sex incidence, biochemical parameters, various etiologies of CRF, types of renal and extrarenal pathology, and the causes leading to death of these patients with CRF and ESRD.
| Materials and Methods|| |
All autopsies performed on patients with CRF and ESRD - (known cases and cases diagnosed at autopsy) at a tertiary care hospital in Mumbai, India, over a period of seven years, from 2005–2012, were included in the study. Patients with known history of CRF and CRF diagnosed at autopsy were both selected for the study. Patients with serum creatinine >2 mg/dL and histology of kidney showing significant renal parenchyma damage or fea tures of ESRD were all included in the study.
Autopsy done on patients presenting with only acute renal failure and all medicolegal autop sies were excluded from the study. Gross fea tures of various organs preserved in formalin for adequate duration were studied. After pre servation, adequate sections from various organs were taken. Sections were studied using stains such as H and E and special stains such as Congo red, periodic acid-Schiff, and Elastic Van Gieson wherever required. Case histories were retrieved by going through indoor case papers.
| Results|| |
A maximum number of CRF patients were in the age group of 56–65 (26%) years, followed by age group of 16–25 (16%) and 46–55 (16%) years.
Out of 50 patients, 29 (58%) were males and 21 (42%) were females. There was a slight male preponderance with male:female ratio of 1.38:1, but the age groups 16–25, 56–65, and 66–75 years showed slight female preponderance.
Common presenting symptoms at the time of admission
Oliguria and anasarca were the most common presenting symptoms followed by breathless- ness, altered sensorium, fever, anorexia, gene ralized fatigue, and chest pain.
Twenty-five patients were on hemodialysis, three patients were advised dialysis, and 24 patients were on treatment either for diabetes or hypertension.
Etiology of chronic renal failure
Chronic pyelonephritis (28%) was the most common cause of CRF observed in our study. This included cases with obstructive as well as nonobstructive pathology. Renal calculi, benign prostatic hyperplasia (BPH), and carcinoma bladder were the causes of obstructive chronic pyelonephritis. HT (22%) was the next most common cause of CRF, followed by diabetes (20%), chronic glomerulonephritis (CGN) (10%), amyloidosis (6%), autosomal dominant polycystic kidney disease (ADPKD) (6%), ischemic (renal artery stenosis 2%), and mul tiple myeloma (2%) were the other causes observed [Table 1]. One patient with ESRD had features of both nonobstructive chronic pyelonephritis and HT (2%) and one had features of both diabetes and HT (2%).
There were three cases of amyloidosis - primary amyloidosis, of which one was due to plasma cell dyscrasia and the patient presented with nephritic syndrome. In two out of three cases, amyloidosis was secondary to pulmonary tuberculosis (TB). Organs such as heart, liver, spleen, adrenal, gastrointestinal system, and kidneys showed amyloid deposits [Table 2].
Blood urea nitrogen of the patients ranged from 29–176 mg/dL. Serum creatinine was in the range of 3.76–26.4 mg%. The lowest hemo globin value was 3.6 g% and highest 13.6 g%.
Urine examination reports were available in 34 patients, out of that 22 patients had protei- nuria, three of which had nephrotic range protei- nuria. Twelve had hematuria, eight had pyuria. Six patients had glucosuria. Ketonuria was present in two patients with diabetic keto- acidosis. Besides, white blood cells, red blood cells and hyaline casts, and granular casts were seen in 16 patients and broad, waxy casts in 5 patients. Calcium oxalate and triple phosphate crystals were seen in three cases.
Ultrasonography abdomen findings were avai lable in 22 cases. Grade I medical renal disease was diagnosed in five cases, Grade II medical renal disease in five cases, Grade III medical renal disease in four cases, renal cal culi in two cases, hydronephrosis in two cases, and two cases were of ADPKD.
Kidney size and weight: Contracted granular kidneys due to benign nephrosclerosis and CGN had an average weight of 80–120 g. The end-stage kidney due to CGN was markedly contracted and weighed only 10 g.
Eight out of the ten diabetic kidneys did not show any apparent reduction in size and weight. In two of these cases, where there was a history of hypertension, kidneys showed a mild reduction in size. In chronic pyelo nephritis, kidneys were asymmetrically con tracted, irregular to U shaped, broad depressed scar. On cut section, scars reaching up to and involving medulla were seen. In six patients of obstructive pyelonephritis due to calculi, two had staghorn calculi. Pelvicalyceal systems were markedly dilated in two cases with marked atrophy of renal parenchyma. Hydro- ureter was seen in four cases. BPH was the cause of obstruction in four cases and carci noma bladder in one case of chronic obstruc tive pyelonephritis.
In autosomal polycystic kidney disease, kid neys were markedly enlarged bilaterally with numerous cyst ranging from few millimeters to 2 cm, containing clear fluid.
Multiple myeloma kidney showed mild enlargement with external surface showing patchy white areas suggestive of infiltration.
Gastric mucosal erosions were seen in five cases and hemorrhagic gastritis in two cases.
Parathyroid dissection was done in 16 cases combined gland weight was <100 g. No evidence of parathyroid hyperplasia seen in any of them.
Left ventricular hypertrophy (LVH) was seen in thirty cases, of which one patient had biventricular hypertrophy and others had asso- ciated left atrial enlargement.
Aorta showed atherosclerosis in 29 cases, of which two had complicated atherosclerosis. Accelerated atherosclerosis was observed in six relatively young age group patients. Coronaries showed atheromatous plaques in 14 cases, with blocks ranging from 30% to 90%. Eight patients had evidence of ischemic heart disease. Fibrinous pericarditis was seen in two cases.
The major cause of death in CRF patients was cardiovascular causes (30%) followed by respiratory causes. The other causes included septicemia and acute febrile illness including malaria. Various causes of death in patients with CRF are shown in [Table 3].
| Discussion|| |
The age and sex incidence of patients in our study were comparable to the other clinical autopsy studies of CRF. Ojo et al and Nzegwu et al in their autopsy studies of CRF observed slight male preponderance and majority of the patients were in the fourth decade.
The Indian CKD registry was set up by the Indian Society of Nephrology in 2005 with the aim to serve as a comprehensive nationwide data warehouse for studying various aspects of CKD. The Indian CKD Registry documents the demographics, etiological spectrum, prac tice patterns, variations, and special charac teristics of CKD. In the clinical study of CKD registry, data of 52,273 adult CKD patients from all zones of the country were analyzed.
In comparison with the US Renal Data System, we had a higher incidence of chronic pyelonephritis, especially in patients in the third and fourth decades and low incidence of diabetic nephropathy. When compared with the autopsy study of 50 CRF patients by Nzegwu et al, our incidence of CGN was much less [Table 1].
In the patients with hypertension, minimum duration of HT was five years. The age of the patients ranged from 20–95 years. Blood pres sure (BP) at admission was ranging from 148/80 to 200/100 mm Hg. Four patients had associated a history of diabetes (random blood sugar on admission ranged 135–336 mg%). In an autopsy study of 94 CRF patients, HT was observed in 59% of patients by Clyne et al.
All diabetic patients were in the older age group (50–75 years). History of duration of diabetes was from 5–9 years. Out of 10 pa tients, seven patients had associated history of hypertension.
Our incidence of CGN was much lower than the other studies., Two cases showed features of membranoproliferative glomerulonephritis, one diffuse proliferative glomerulonephritis, and in both cases, original disease could not be identified, and kidney showed features of ESRD. These patients were on hemodialysis for CGN.
In the present study, interstitial nephritis/ chronic pyelonephritis was the cause of CRF in 14 patients (28%). Ojo et al found chronic pyelonephritis as cause of CRF in 9% pa- tients. Mittal et al in a clinical study of CRF patients observed interstitial nephritis in 22.9% patients.
Patient age ranged from 20–85 years. Three patients had a history of diabetes. No case of drug-induced interstitial nephritis was observed in our study.
In two cases of ESRD, one had a history of HT and diabetes and another patient had HT with chronic pyelonephritis. In these two cases, exact cause of CRF could not be ascertained on histology, as sections showed end-stage kidney.
We had three cases of ADPKD leading to CRF. Age of patients ranged from 27–44 years. Out of these, one patient was hypertensive, one patient had LVH, and one patient died of raised intracranial tension following intracranial bleeding. Associated liver cyst found in one case. No cysts were observed in any other organ.
In an autopsy study of 41 cases of ADPKD patients, Chan observed that 46% of patients had reached ESRD at the time of death. Intra- cranial bleed was cause of death in 6 out of 41 patients. LVH was found in 59% patients. Cysts in liver found in 63% of patients.
The case of primary amyloidosis was due to plasma cell dyscrasia and the patient presented with nephritic syndrome. In two out of three cases, amyloidosis was secondary to pulmo nary TB. Organs such as heart, liver, spleen, adrenal, gastrointestinal system, and kidneys showed amyloid deposits. Mehta et al and Shah et al in the study of amyloidosis cases (autopsy and biopsy) observed that majority of the cases were secondary amyloidosis due to TB. Two of our patients died of pneumonia and one due to congestive cardiac failure.
One of the patients of our study was a 40- year-old female, a known case of renal artery stenosis with a history of renal artery angio- plasty done 10 years back. Her BP was 156/90 mm Hg on admission, died of congestive cardiac failure, and aorta showed complicated atherosclerosis at autopsy.
One patient was a 60-year-old male who presented with exacerbation of chronic obs tructive pulmonary disease. On investigation, he was found to have hemoglobin of 6.6 g% and serum creatinine level of 4.5 mg/dL. CT abdomen showed osteolytic mass in the pelvis and multiple punched-out bony lesions in the pelvic bones. Histopathological examination of mass showed features of multiple myeloma. Renal histopathological examination showed atrophic and dilated tubules with fractured myeloma cast, interstitial fibrosis, and periglo- merular fibrosis. Patient died of pneumonia.
In an autopsy study of 77 patients dying from complication of plasma cell dyscrasias, Herrera et al found myeloma cast nephropathy in 22 cases.
The major cause of death in CRF patients was cardiovascular causes (30%) which was concurrent with the US renal data system [Table 4]. However, we had much higher in fectious causes of death, especially pulmonary- bacterial pneumonia and TB.
Clyne et al found CCF in 37%, acute myo- cardial infarction in 13%, and tamponading pericarditis in 8% of cases as cardiac cause of death in 94 autopsied cases of CRF. Cardiac cause of death was seen more in young pa tients, age ranging from 22–50 years. They had associated anemia, diabetes mellitus, and/ or HT and LVH.
Infections were the next most frequent causes of death after congestive cardiac failure in our study. One patient of multiple myeloma died of respiratory failure following pneumonia, as multiple myeloma patients are more suscep tible to infection. Oshima et al in autopsy study of 52 cases also noted, infection as one of the major causes of death in multiple mye loma patients.
| Limitation of the study|| |
Small sample size since it was an autopsy study.
| Conclusion|| |
The ESRD patients are faced with a broad spectrum of cardiovascular and infectious di sease. Analysis of etiology and cause of death in CRF patients helps in preparing guidelines for counseling and planning therapy for the patients as well as screening and treatment of the associated septic complications, thereby reducing the mortality and morbidity. The renal histomorphological features observed in autopsy kidneys of CRF, helps in the compa rative evaluation of kidney biopsies of CRF patients.
Conflict of interest: None declared.
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Department of Pathology, Lokmanya Tilak Municipal Medical College and Hospital, Sion, Mumbai, Maharashtra
[Table 1], [Table 2], [Table 3], [Table 4]