Clinico-Pathological Conference 30 Nov 2007

Case scenario A 60-year old man presented to the local hospital’s Accident & Emergency Department with a 3-day history of progressively severe back pain, malaise, fever and rigors. He also complained of cloudy and blood-stained urine as well as a burning sensation on micturition.

He had been diagnosed of adult-onset diabetes mellitus 10 years previously, but has not been compliant with his diabetic medications. He smokes 15 cigs/day for the last 20 years and has a history of hyperlipidaemia. He had also been suffering from UTIs over the years and the episodes had become increasingly frequent. His case notes revealed that the last 3 UTIs over the previous 6 months were caused by Proteus mirabilis.

Over the last few weeks, he was also experiencing intermittent back pain associated with blood- stained urine but had not sought medical attention until now. On presentation, he was found to be dehydrated and pyrexial. He had bilateral renal angle tenderness (L>R) and suprapubic discomfort. His random blood glucose level was 14 mmol/L and a dipstick urinalysis was performed.

Urinalysis Protein, blood, nitrites, WBCs in the urine.

A presumptive diagnosis of pyelonephritis and poor glycaemic control was made. MSU and blood cultures were sent to the laboratory. Blood was also taken for FBC,HbA1C, electrolytes, urea, creatinine, glucose etc. A 24-hour urine collection was initiated to assess renal function and creatinine clearance. He was commenced on IV fluids and empirical antimicrobial therapy of IV co-amoxiclav.

Q. What is the definition of a complicated UTI? A. A complicated UTI is an infection occurring in a patient with structural or functional abnormalities of the voiding mechanism.

Q. Can you name examples of such abnormalities? A.1) Structural abnormalities: - calculi (renal, bladder, prostatic) - strictures (urethra, ureter) - prostatic obstruction (benign, neoplastic) - vesicoureteric reflux - neurogenic bladder (paraplegia, diabetes) - indwelling urinary catheter

A. 2) common underlying diseases: - diabetes mellitus - sickle cell anaemia - polycystic renal disease - renal transplantation - immunosuppressant therapy

Q. What organisms are commonly associated with complicated UTIs? A.Gram-negative bacteria: - Escherichia coli - Klebsiella; Enterobacter; Proteus; Serratia - Pseudomonas aeruginosa; Acinetobacter Gram-positive bacteria: - Enterococcus - Staphylococcus aureus; coag-neg staph Yeast: - Candida albicans

Q. What are the clinical implications of complicated UTIs? A. Such infections are exceedingly difficult to eradicate without correcting the underlying defect or removing the foreign body. Patients with complicated UTIs are at increased risk for severe renal damage, bacteraemia, sepsis and increased mortality.

Q. What are the pathological features of chronic pyelonephritis? A.chronic cortical scarring tubulointerstitial damage deformity of the underlying calyx

Chronic Pyelonephritis The large collection of chronic inflammatory cells here is in a patient with a history of multiple recurrent urinary tract infections. Both lymphocytes and plasma cells are seen in this case of chronic pyelonephritis. It is not uncommon to see lymphocytes accompany just about any chronic renal disease: glomerulonephritis, nephrosclerosis, pyelonephritis. However, the plasma cells are most characteristic for chronic pyelonephritis.

Acute Pyelonephritis -Comparison Note the numerous PMNs in the tubules. The neutrophils can collect in the distal tubules and be passed in urine as WBC casts.

Acute Pyelonephritis -Comparison Areas of hemorrhage and suppuration grossly.

Q. What other renal complications may result from poorly-controlled diabetes mellitus? A.Albuminuria / proteinuria Nodular / diffuse glomerulosclerosis Papillary necrosis Arteriolosclerosis, arteriosclerosis Atherosclerosis Perinephric abscess

Nodular glomerulosclerosis & arteriolosclerosis

The following are the MSU results: MicroscopyWCC>1000 wcc/mm^3 RCC200 rbc/mm^3 CulturePure growth of: Proteus mirabilis >10^5 orgs/ml SusceptibilityAmpicillinR Co-amoxiclavR TrimethoprimR NitrofurantoinR CiprofloxacinS GentamicinS CefotaximeR

Q. What is your interpretation of the MSU results? A.Significant pyuria and haematuria associated with urinary tract infection caused by a fairly resistant Proteus mirabilis. In view of the above results, a diagnosis of Proteus mirabilis UTI was made. He was continued on IV fluids and his antimicrobial therapy was changed to ciprofloxacin.

Over the next 2 days, his clinical condition improved significantly. His temperature came down to 37.5 degC and his rigors stopped. He was less nauseated and his appetite improved. However, he continued to have intermittent pain around the left renal angle and flank; he also noticed that although the urine has become less cloudy, the haematuria has not resolved despite antibiotic treatment.

Q. In view of his recent history and persistent symptoms, what further investigations would you consider? A.Radiological investigations eg: - ultrasonography; - KUB x-ray; intravenous urogram; - CT scan; retrograde pyelogram; etc. Repeat microbiological tests ie. MSU ?Cystoscopy

Repeated dipstick urinalysis confirmed the presence of blood in his urine. In view of the persisting back pain and haematuria with the background of poorly-controlled diabetes and recurrent Proteus UTI, further investigations were arranged. A KUB x-ray and CT of kidneys & urinary tract were performed.

KUBCT Scan

Radiological diagnosis: bilateral nephrolithiasis In view of recurrent Proteus UTIs: struvite stone?

Staghorn calculus with areas of necrosis and haemorrhage.

Q. What are the different types of renal stones? A. Calcium oxalate / apatite stones (~75%) Uric acid stones (~10%) Struvite (magnesium ammonium phosphate) stones (~10%) Cystine stones (~2%) Others

Q. Discuss the management of renal colic. History, physical examination, urinalysis ↓ Presumptive diagnosis managementdiagnosis ↓ ↓ IV fluids, analgesiaradiological tests, etc. Treatment Eg. Conservative management; Extracorporeal shock wave lithotripsy (ESWL) Percutaneous nephrostolithotomy

↓ Stone analysis; Diagnostic evaluation for cause of nephrolithiasis ↓ Preventive therapy Eg. High fluid intake, dietary changes, drug Rx.

The patient underwent ESWL to have the renal calculi removed. Following the procedure, he received a course of ciprofloxacin to eradicate any persisting bacteria. He was informed of the importance of maintaining good glycaemic control and was also referred to an endocrinologist for further management of his diabetes mellitus.