History Salient Features Physical Exam A 50 y/o was referred for evaluation of azotemia. 10 yrs ago, he experienced sudden onset of pain on his right big toe. His serum uric acid was elevated. He was diagnosed to have gout and was prescribed medication but he was poorly compliant. The gouty attacks recurred lately hence, he decided to undergo thorough check-up. He denies dysuria, flank pain or hesitancy. He has nocturia. BP is 120/70 Obese numerous tophi in his metacarpo-phalangea l elbow joint no edema A 50 y/o obese male with longstanding hyperuricemia Patient experiences nocturia but there is no dysuria, flank pain or hesitancy, and edema BP is 120/70 Numerous tophi in his metacarpo-phalangeal elbow joint

Clinical Impression Gouty nephropathy Patients with prolonged forms of hyperuricemia are predisposed to a more chronic tubulointerstitial disorder Distinctive feature: presence of crystalline deposits of uric acid and monosodium urate salts in kidney parenchyma Clinically, gouty nephropathy is an insidious cause of renal insufficiency. Early in its course GFR may be near normal despite focal morphologic changes in medullary and cortical interstitium and diminished urinary concentrating ability - These deposits not only causes intrarenal obstruction but also incite an inflammatory response leading to lymphocytic infiltration, foreign-body giant cell reaction and eventual fibrosis Gout is a metabolic disease resulting from an increased body pool of urate due to an overproduction or underproduction of uric acid. It is characterized by episodic arthritis due to the deposition of monosodium urate crystals in joints and connective tissue tophi (just as seen in our patient), and the risk for deposition in the kidney interstitium or uric acid nephrolithiasis. Patients with prolonged forms of hyperuricemia (just as in the case of our patient who was diagnosed to have gout 10 years ago, was poorly compliant with his medications and now experiencing a recurrence of gouty attacks) are predisposed to a more chronic tubulointerstitial disorder, often referred to as gouty nephropathy, which is also known as chronic uric acid nephropathy. The distinctive feature of this type of disease is the presence of crystalline deposits of uric acid and monosodium urate salts in the kidney parenchyma. These deposits not only causes intrarenal obstruction but also incite an inflammatory response leading to lymphocytic infiltration, foreign-body giant cell reaction and eventual fibrosis. Clinically, gouty nephropathy is an insidious cause of renal insufficiency. Despite the focal morphologic changes in the medullary and cortical interstitium, proteinuria and diminished urinary concentrating ability, the glomerular filtration rate may be near normal.

Algorithm/Sequence of Events Renal Deposition of Urates Pelvic Calculi Parenchymal Urate (microtophi) Tubular Uric Acid (obstruction) Gout Renal Insufficiency

Differential Diagnosis Diabetic Nephropathy Kimmelstiel-Wilson syndrome a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli characterized by nephrotic syndrome and diffuse glomerulosclerosis.

Spectrum of Disease Diagram Lower testing threshold Upper testing threshold Pretest probability Do nothing. Rule out the disease Treat the patient without waiting for more information Do additional diagnostic exams to confirm diagnosis (testing zone) 20 % 70% % 41%