Patient 1

A 30-year-old woman presented to hospital with bilateral hand paraesthesia and a serum potassium level of 2.9 mmol/L (reference range [RR], 3.5–5.0 mmol/L). She denied taking medications and had no significant past medical history. However, 3 months before admission, she had presented to her general practitioner complaining of anorexia, nausea, lethargy, fevers and aches. An erythrocyte sedimentation rate (ESR) of 91 mm/h (RR, 7–18 mm/h) and a serum creatinine level of 0.106 mmol/L (RR, 0.030–0.110 mmol/L) were noted. (Twelve months previously, her serum creatinine level had been 0.073 mmol/L.) Then, 1 month before admission, she had developed blurred vision due to anterior uveitis, diagnosed by an ophthalmologist, and was treated with topical steroids. In the intervening period, she had lost 12 kg in weight.

A normochromic, normocytic anaemia was now present (haemoglobin level, 103 g/L; RR, 115–165 g/L), and her serum creatinine level was 0.230 mmol/L. The hypokalaemia was corrected, and she was discharged with a referral to the renal outpatient clinic.

In clinic, her blood pressure was 140/85 mmHg, but the physical examination was otherwise normal. Repeat laboratory tests showed: creatinine, 0.250 mmol/L; potassium, 3.1 mmol/L; bicarbonate, 17 mmol/L (RR, 23–31 mmol/L); and phosphate, 0.64 mmol/L (RR, 0.60–1.40 mmol/L). Urine microscopy showed no leukocytes, erythrocytes or casts. Urine pH was 7.0, with glucosuria on dipstick. Protein excretion was 0.9 g/day (RR, < 0.15 g/day). Autoimmune markers were negative, including antinuclear antibody, antineutrophil cytoplasmic antibody, antidouble-stranded DNA antibody, and antibodies to extractable nuclear antigens. Serum calcium and angiotensin-converting enzyme (ACE) levels were normal. A chest x-ray and renal ultrasound were unremarkable. A renal biopsy showed acute interstitial nephritis and chronic renal damage (Figure A).

After taking prednisolone 60 mg/day and concurrent phosphate, bicarbonate and potassium supplements for 4 weeks, her serum creatinine level fell to 0.130 mmol/L. The dose of steroids was reduced

gradually over 4 months and renal function remained stable. Shortly after stopping prednisolone, her eye symptoms recurred. Ophthalmological examination revealed a bilateral visual acuity of 6/4, keratic precipitates, posterior synechiae and perilimbal injection, consistent with anterior uveitis (Figure B). This responded to topical steroids.

Patient 2

A 34-year-old woman was referred to the renal clinic by her general practitioner, with a creatinine level of 0.190 mmol/L, normochromic, normocytic anaemia (haemoglobin level, 110 g/L), and an elevated ESR (120 mm/h). She gave a 1-month history of weight loss (15 kg), with anorexia, nausea, arthralgias, myalgias, fatigue and fevers. She had mild asthma, which was being treated with salbutamol, and took no other medications. Physical examination was unremarkable.

Repeat laboratory tests 1 week later showed a serum creatinine level of 0.250 mmol/L. Urine microscopy showed no leukocytes, erythrocytes or casts. Proteinuria was absent and a renal ultrasound gave normal results. A renal biopsy revealed granulomatous acute interstitial nephritis with multinucleated giant cells (Figure C). Her serum calcium and ACE levels were normal, and a chest x-ray was unremarkable. Oral prednisolone 60 mg/day was commenced.

One week later, her constitutional symptoms and renal function markedly improved. Repeat tests showed: creatinine, 0.120 mmol/L; potassium, 2.9 mmol/L; and phosphate, 0.40 mmol/L. Glucosuria was detected on urine dipstick analysis. All autoimmune markers and HLA-B27 were negative. Potassium supplementation was commenced.

After the prednisolone dose was reduced to 2.5 mg/day over 2 months, she developed bilateral red and painful eyes, photophobia and watery discharge. Ophthalmological examination showed bilateral anterior uveitis, with a visual acuity of 6/9 bilaterally, perilimbal injection, keratic precipitates, anterior chamber cells 3+, and posterior synechiae. The uveitis resolved with topical steroids and cycloplegic agents. Her serum creatinine level remained stable without steroid dose adjustment.

A: Renal biopsy specimen (Patient 1) showing an interstitial infiltrate of lymphocytes, plasma cells, histiocytes and eosinophils, without granulomas. There is prominent tubular atrophy and wide separation of tubular structures due to interstitial fibrosis (haematoxylin–eosin stain, original magnification x 200).

B: Photograph of the right eye of Patient 1, with the thick arrow showing pupil irregularity and posterior synechiae, and thin arrows showing inflammatory perilimbal injection. Keratic precipitates and anterior chamber cells are best appreciated on slit lamp examination.

C: Renal biopsy specimen (Patient 2) showing tubulointerstitial mononuclear infiltrate with non-caseating granulomas and multinucleated giant cells (large arrows) (haematoxylin–eosin stain, original magnification x 200). Inset: Small arrows highlight eosinophils with typical bilobed nuclei (x 400).