CHRONIC INTERSTITIAL NEPHRITIS FOLLOWING PARENTERAL COPPER SULFATE POISONING

Abstract

A 21-year-old male patient was admitted with acute renal failure and intravascular hemolysis following suicidal parenteral copper sulfate poisoning. He developed metabolic acidosis and septicemia; and was treated with intensive hemodialysis, blood transfusions and antibiotics. After remaining anuric for 4 weeks, his urine output gradually increased. However his renal functions improved only partially. Renal biopsy done 8 weeks after the episode showed chronic tubulo-interstitial nephritis (CIN). This is the first reported case showing CIN following acute copper sulfate intoxication.

• Chronic interstitial nephritis
• Copper sulfate poisoning

INTRODUCTION

Copper is an essential trace element and functions as a cofactor for oxidative enzymes, such as catalase, peroxidase, cytochromeoxydase and dopamine-β-hydroxylase [[1]]. However it can cause acute and chronic intoxication. Ingestion of copper sulfate with suicidal intent is common in India and Bangladesh. Since it is used as an insecticide, in leather manufacturing, to bind color to fabrics and in chemistry laboratories in colleges, it is available freely and cheaply [2-4]. Acute poisoning has also been reported in patients undergoing dialysis when copper tubing was used in heating coil [[5]]. However, only one case of parenteral copper sulfate poisoning has been reported so far [[6]]. We report a case of intravenous copper sulfate poisoning following a suicidal attempt.

CASE REPORT

A 21-year-old male patient, a pharmacist by occupation, was admitted from the casualty with acute renal failure. The patient had became depressed following a failed love affair and decided to commit suicide. Three days prior to admission he dissolved a small quantity of copper sulfate in 5 mL of tap water and injected it intravenously into his left antecubital vein. The next day his urine output decreased and he started passing dark colored urine. There was no history of hemetemesis, vomiting or malena. A day prior to admission he became anuric. He admitted to his parents about his suicidal attempt and was brought to the emergency services of the hospital.

On admission he was conscious but drowsy. He was afebrile, pulse – 110/min, BP – 130/80 mm of Hg and respiratory rate – 26/min. There was marked pallor and moderate icterus. Cardiovascular, respiratory and abdominal examinations were essentially normal. Laboratory data revealed hemoglobin 6.5 gm%, total leukocyte count 11000/mm³, platelet count 200,000/mm³ and reticulocyte 10%. The plasma hemoglobin was 32 mg%. Blood urea was 110 mg/dL, creatinine 2.2 mg/dL, sodium 135 meq/L and potassium 4.9 meq/L. Liver function tests were bilirubin 2.8 mg/dL, SGOT 74 U/L and SGPT 115 U/L. CPK was 1100 U/L and LDH 758 U/L. The serum copper level was 195 μg/dL. Urine examination revealed protein 3+ and presence of hemoglobin 3+. Analysis of blood gases showed pH 7.2, PCO₂ 25.5 mmHg, PO₂85 mmHg and bicarbonate 16 meq/L.

In the hospital he remained anuric. His sensorium worsened and he became more acidotic. Hence he was given hemodialysis with blood transfusions. He remained anuric for 4 weeks and his serum creatinine rose to a maximum of 12 mg% during this period. He was dialyzed 3–4 times a week. Thereafter his urine output gradually increased. His serum copper level a month after the incident was 50 μg/dL. He became dialysis independent after 6 weeks and the serum creatinine started declining gradually. However it remained static at 5 mg%. Hence 8 weeks after the incident a percutaneous renal biopsy was done. It showed marked patchy tubular atrophy with interstitial fibrosis and mild focal chronic interstitial inflammation. Some tubules showed regenerating epithelial cells with multilayering and mitosis. There appeared to be a predominant loss of proximal tubules. Several atrophic tubules were dilated with granular and hyaline casts. The glomeruli and blood vessels were unremarkable. The findings were suggestive of chronic tubulo-interstitial nephritis (CIN) with significant increase in chronicity indices (Figure 1). The prognosis was explained to the patient. He was discharged with conservative treatment of chronic renal failure and advised to follow in the renal clinic at regular intervals.

Figure 1. Photomicrograph of the kidney biopsy showing focal dilatation of proximal tubules with granular casts and lining of low cuboidal epithelium of regenerating epithelium. The glomerulus is unremarkable. There is patchy tubular atrophy with interstitial fibrosis (F). (H&E ×120).

DISCUSSION

Intentional copper sulfate ingestion to commit suicide is common in India, seen mainly in farmers and sometimes in science students, who have easy access to a chemistry laboratory. Our patient was a pharmacist by occupation and he dissolved a small quantity of copper sulfate in 5 mL of tap water and self injected into the left antecubital vein. He developed oliguria, intravenous hemolysis, acute renal failure and hepatic failure over the next two days. There were no symptoms of nausea, vomiting, diarrhoea or hemetemesis in our patient as is common following copper sulfate ingestion [[2]] and also in the only other case of parenteral copper sulfate poisoning [[6]]. The patient was not administered any chelating agent as he reported after three days with established acute renal failure. Hemodialysis is not known to be beneficial in the treatment of copper sulfate poisoning [[7]]. However, it was done in our patient as part of supportive treatment of acute renal failure. Copper sulfate poisoning is known to have the highest mortality amongst the other commonly used poisons [3-4]. Our patient was very sick initially with severe anemia due to intravenous hemolysis, acute renal failure and hepatic failure, but gradually stabilized over a period of a month.

He had a prolonged period of anuria as compared to the study by Chugh et al [[2]], and his renal functions showed only partial improvement. Hence, after a period of eight weeks, renal biopsy was done with a possibility of acute cortical necrosis in mind, which rarely occurs [[8]]. However the kidney biopsy showed features of CIN (with relatively preserved glomeruli). This finding has not been reported so far in copper sulfate poisoning. The commonest renal lesion described is acute tubular necrosis (ATN) and a single case of interstitial granuloma [[2]]. The mechanisms of ATN proposed are intravenous hemolysis, hypotension and direct tubular toxicity due to copper released from hemolyzed RBCs, which is deposited in the tubules of the kidney [[2]]. In our patient it is possible that very high levels of blood copper immediately following bolus intravenous copper sulfate administration may have caused irreversible damage to the renal tubules resulting in CIN. It is pertinent to note that in the only other patient with parenteral poisoning [[6]], the serum creatinine 6 weeks after the intoxication was 1.7 mg/dL, which is still not completely normal. It is possible that this patient too may have developed some chronic changes, but renal biopsy unfortunately is not available. The possibility of pre-existing CIN in our patient cannot be completely ruled out, as we do not have any records of renal function prior to the incident. However, in all probability the serum creatinine was well within normal limits earlier, since 2 days after the intoxication (when he already had oliguria) it was only 2.2 mg%.

In conclusion we present a case of suicidal parenteral copper sulfate poisoning, who developed ARF and hepatic failure. He had a prolonged period of anuria and renal recovery was incomplete. He became dialysis independent after six weeks, but kidney biopsy showed evidence of CIN.