Acute Graft Dysfunction Due to Pyelonephritis: Value and Safety of Graft Biopsy

Introduction

Urinary tract infections are the most common infection following renal transplant.[[1]] Renal transplant recipient have 28% to more than 90% incidence of urinary tract infection occurring after hospital discharge.[[2]] Risk factors of development of UTI include indwelling catheter, urinary bladder dysfunction especially in diabetic patients, anatomical abnormality, renal insufficiency, nutritional deficiency, and possibly rejection and immunosuppression.[[3]] It can lead to graft dysfunction and may induce graft loss in severe pyelonephritis.[[4]]

Morbidity associated with urinary tract infection happens to be related to the timing of episode during post transplant period. Infection occurring during early transplant period is generally more serious. It can cause a graft dysfunction and even graft loss. While infection developing 3–6 months after transplantation are more benign and rarely associated with bacteremia.[[3]]

The role of renal allograft biopsy in patients with suspected pyelonephritis and graft dysfunction is not well defined. This study tries to analyze its value and safety in a living related transplant program.

Method

We retrospectively analyze data of all the patients who had allograft biopsy in the setting of graft dysfunction and urinary tract infection during period of January 1997 to December 1997. All patients who developed graft dysfunction underwent a detailed clinical history, physical examination, routine blood biochemistry, urine analysis, and culture. All patients with suspected acute rejection and those patients with urinary tract infection who did not respond to antibiotics within 48 h went through allograft biopsy. The allograft biopsy was performed with 18-gauge needle using a spring-loaded biopsy gun.

Results

Six patients (3 male and 3 female) were found to have graft dysfunction in association with urinary tract infection. Three patients developed end stage renal failure due to unknown cause, one had renal calculus disease and two had bladder outlet obstruction as primary pathology. Four patients had one haplotype and two patients had identical match on HLA typing. Immunosuppression comprised of cyclosporine, azathioprine, and prednisolone in all six patients. All of these patients had one episode of biopsy proven acute cellular rejection except one patient who had two episodes of acute rejection. Steroid pulse therapy was given to all patients for acute rejection, two patients (patient 1 and 2) required biological agent for steroid resistant rejection. All patients were pyrexial on admission. Causative organism, histological appearance, treatment, and response to treatment are described in Table 1.

Table 1.

Patients	Age/ sex	Duration post Tx	Pyuria	Urine C/s before Bx	Urine C/s after Bx	Biopsy appearance	Biopsy complications	Treatment	Fall in Cr	Resolution of infection
1. RH	15/M	11 wks	Num WBCs	MIBG	Pseudo- monas	Ac. Pyelonephritis	none	Augmentin + Aztreonam + Amikacin + Fluconazole	Not seen	Died in septicemia
2. FK	30/F	10 wks	4–6	Pseudomonas	Pseudo- monas	Micro abscess in tubules	none	Augmentin + Aztreonam + Fluconazole	Further rise	Died in septicemia
3. ES	15/F	10 wks	Num WBCs	MIBG	Pseudo- monas	Ac. Pyelonephritis	none	Ceftazidime + Amikacin	Static	Fever and other symptoms
4. AM	22/F	12 wks	Num	MIBG	Pseudo- monas	Ac. Pyelonephritis	none	Aztreonam + Ceftazidime	Subsided to previous level	In 2 weeks
5. BA	30/M	6 wks	10–12	Pseudomonas	—	Ac. Pyelonephritis	none	Aztreonam + Ceftazidime	Static with late improvement	After 1 month of antimicrobial therapy
6. AJ	25/M	3 yrs	10–12	Klebsiella	—	Micro abscesses + Ac. rejection	Gross haematuria	Oflaxacin + pulse steroid + OKT3	Static with late improvement	In 2 weeks

MIBG = Mixed insignificant bacterial growth.

Discussion

Renal biopsy remains the most definitive and diagnostic test of graft dysfunction. It can change the diagnosis and thereby alter the management in upto 40% of cases.[[5]] Fortunately it is safe procedure and a study at Massachusetts General Hospital on 1460 allograft biopsy did not reveal any graft or patient loss.[[6]]

The presence of an active untreated urinary tract infection is considered a contraindication to renal biopsy, in view of potential communication between collecting system and possible hematoma, with consequent catastrophic infection of hematoma. However allograft pyelonephritis can present as acute graft dysfunction and can happen in absence of pyuria,[[7]] which makes it difficult to differentiate from acute rejection. In case where diagnosis is not clear by non-invasive method biopsy is helpful. Sometime it can reveal presence of another pathology as it happened in one of our patient. We did not experience any major complication leading to patient or graft loss, and it spared the patients from having unnecessary immunosuppression.