Spectrum of Renal Injury in Pregnancy Induced Hypertension : South Indian Experience

The literature, particularly from India is scarce on the renal effects of glyphosate poisoning.Glyphosate causes toxicity not only after its ingestion, but also after dermal exposure, by inhalation route and upon eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis– the first report after glyphosate consumption and acute kidney injury. Introduction :The literature, particularly from India is scarce on the renal effects of glyphosate poisoning. Commercial glyphosate-based formulations range from 41% or more concentration of glyphosate to 1% glyphosate formulations. The latter is marketed for domestic use. The formulations consist of an aqueous mixture of the isopropylamine (IPA) salt of glyphosate, a surfactant, and various minor components. Polyoxyethyleneamine is commonly used as a surfactant.Glyphosate causes toxicity not only after its ingestion, but also after dermal exposure, by inhalation route and upon eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis– the first report after glyphosate consumption and acute kidney injury. Case report :A 30-year-old gentleman has consumed glyphosate (Hexagor 71%) with an intention to self-harm. He consumed 15mL.At a primary health centre gastric lavage was done withina hour. On the same day evening he developed body pains, oliguria and generalized erythema. The skin lesions later evolved into multiple discrete, closely set sterile pustules on flexures like elbows, axillae, and nape of neck. There was erythematous maculopapular rash on lower abdomen and upper thigh. The mucosae were normal. Within a day he developed anuria and pulmonary oedema. The skin lesions also progressed to widespread large bullous lesions on limbs and trunk. There were bleeding lip and oral ulcers, redness and watering of eyes and scrotal moist erosion. The Nicolsky sign was positive. At admission the blood pressure was 130/80 mm Hg. The patient had normotension during entire hospital stay. The investigation were, serum creatinine: 10.1 mg/dL, blood urea: 201 mg/dL, serum sodium: 135 mEq/L, serum potassium: 6.2 mEq/L, haemoglobin: 13.2 g/dL, total leucocyte count: 6800/mm and platelet count: 60,000/mm, total bilirubin: 0.7 mg/dL, SGOT: 77 U/L, SGPT: 46 U/L, serum alkaline phosphatase: 75 U/L, serum creatinine phosphokinase: 215 IU/L, serum lactate dehydrogenase: 2579 U/L, serum cholinesterase: 1589 U/mL, serum pH: 7.2, serum bicarbonate 11.5 mmol/L and urine examination: albumin: 2+, pus cells: 1-2/hpf, red blood cells: 0-1/hpf and tubular cast present. Ultrasound abdomen revealed, right kidney: 10.2 x 3.4 cm and left kidney: 10.4 x 3.2 cm. A 4 mm punch biopsy from right forearm revealed stratified squamous epithelium with spongiosis and exocytosis, vacuolar alterations of basal keratinocytes and there was moderate perivascular mononuclear infiltration in papillary dermis. It was consistent with toxic epidermonecrolysis. He was initiated haemodialysis and received eight sessions of haemodialysis before the urine output improved. He was discharged on day 24 after the consumption with normal serum creatinine and blood urea. At a follow up consultation after three months the serum creatinine and blood urea were 1.0 and 24 mg/dL respectively. Conclusion :It is difficult to separate the toxicity of glyphosate from that of the formulation as awhole or to determine the contribution of surfactants to overall toxicity. Experimental studies suggest that thetoxicity of the surfactant, polyoxyethyleneamine (POEA), is greater than the toxicity of glyphosate alone andcommercial formulations alone. Ingestion of >85mL of the concentrated formulation is likely to cause significanttoxicity in adults. In Lee series the mean estimated fatal ingestion was330 mL, while survivors had a mean dose of 122 mL. In plants, glyphosate disrupts the shikimic acid pathway. It results in deficiency of 5enolpyruvylshikimate-3-phosphate production which leads to reductions in protein synthesis and plant growth and death of the plant occurs in 4-20 days.The mechanism of toxicity of glyphosate in mammals is thought to be uncouplingof oxidative phosphorylation. Based on animal studies, it was found that only 30% is absorbed from gastrointestinal tract. The peak plasma concentrations of glyphosate are attained at1–2 hours. 6, 7 The small intestine, colon, kidney and bone are thesites of distribution.The major quantity of glyphosate is excreted unchanged in the urine.In two reports of human poisoning the peak plasma glyphosate concentration reached within 4 hours, the concentrations being almost undetectable by 12 hours. The plasmaglyphosate concentrations 1000 mg/Lto 1600 mg/L have been encountered. 9 Gastrointestinal corrosive effects, with mouth, throat and epigastric pain and dysphagia arecommon. Respiratory distress, impaired consciousness, pulmonary oedema, cardiogenic shock, arrhythmias might appear. Bradycardia and ventricular arrhythmias are often present preterminally. Cardiovascular collapse is a major cause of death after glyphosate exposure, 10, and patients respond poorly to conventional fluid and vasopressor therapy. 13 Skin exposure resulted in several different manifestations. Skin contact with glyphosate had caused irritationand contact dermatitis. Chemical burns that later led to appearance of erythematous macules that developed into bullae within 24 hours was reported. Facial swelling, paresthesiae andperiorbitaloedema and ageneralisedpompholyx were all reported.Our patient had ingested the glyphosate. It is possible, ours is the first report of toxic epidermal necrolysis after consumption of glyphosate. Renal and hepatic impairment are also frequent and usually reflect reduced organ perfusion, although a direct toxic effect of glyphosate or surfactant may contribute. Similarly, hypovolaemia, cardiogenic shock and/or acidosis may also give rise to acute kidney injury. The precise contributions of both the surfactant and glyphosate to herbicide toxic effects in humans remain unknown. The clinical features attributed to surfactant toxicity include vomiting, diarrhea, hemolysis, hypotension, alteredmental status, and pulmonary edema. The clinical features like metabolic acidosis and CNS depression, nephrotoxicity, may be primarily attributed to the glyphosate itself. Management is symptomatic and supportive. Gastric lavage may be considered if a lifethreatening amount of a concentrated glyphosate formulation has been ingested within 1 hour.Activated charcoalmay adsorb the surfactant component of glyphosate. Decontamination with activated charcoal should beundertaken in those with a protected airway and who present early. Use of activated charcoal in patientspresenting > 1 h after serious ingestion should be considered but remains controversial. Early invasivemonitoring, earlyventilatory and haemodynamic support and maintenanceof euvolaemia should all be instituted with alacrity. Hypotension secondary to fluid loss should be treatedappropriate use of crystalloids, colloids and blood products. Ionotropes may also be employed. Metabolic acidosis should be treated with quickly with sodium bicarbonate infusion. Haemodialysis has not been preferred in patients of glyphosate intoxication for the reasonhaemodialysiscould not remove the surfactant, which may be partially responsible for the toxicity,due to its large molecular size. However, haemodialysis does remove glyphosate. 24 Haemodialysis may improveacidosis and hyperkaelemia. The literature search revealed, that in Lee’s series three patients were commenced on haemodialysis for acute kidney injury. All of these patients died. In Stella’s series, both the patients initiated on renal support died. There were only a few published reports of successful haemodialysis in patients who ingested glyphosate. In one patient the daily haemodialysis was instituted for the treatment of pre-renal failure consequent to a massive loss of gastrointestinal fluid three days after ingestion.In another report, two patients exhibited unresponsive hemodynamic states despite aggressive treatment. Bothpatients progressed to an anuric state. Haemodialysis was conducted due to hyperkalemia in one patient and due to metabolic acidosis in second patient. The authors could not entirely dismiss that the hypovolemiawas secondary to gastrointestinal fluid loss as the cause of their hypotension. 18 Our patient had neither gastrointestinal cause nor hypotension due to any other reason to account for acute kidney injury. We did not perform a renal biopsy; for there was no indication. The timing of rise and fall of serum creatinine and presence of tubular cast points towards a possibility of acute tubular necrosis. Our patient recovered completely from acute kidney injury highlighting a possible role of haemodialysis in the management of glyphosate poisoning.