The value of the graft biopsy in the care of renal transplant patients.A Date
Department of Pathology, Christian Medical College & Hospital, Vellore, India., India
Keywords: Biopsy, Needle, Graft Rejection, pathology,Human, Kidney Transplantation, pathology,Sensitivity and Specificity,
This presentation is not a review of the pathology of the renal allograft, which is described in all nephrology texts and given in great detail in books on renal pathology. Instead, this subject will be covered practically by presenting an analysis of 78 consecutive renal allograft biopsies, illustrating the value of biopsies in such patients. The biopsy arises from a clinical question. The question is formulated with the knowledge of the patient's clinical condition, investigation results and the response to any therapeutic measures already instituted to rectify the complaints. The biopsy should be examined by the pathologist initially, without reference to clinical information and a morphological diagnosis arrived at. This morphological diagnosis is an unbiased record of all abnormalities seen. An attempt should then be made to correlate the clinical details provided with the structural changes and preferably following discussion with the clinicians.
A final diagnosis is then made and any treatment available, given. Further, in an ideal situation a follow up on the patient a progress is also communicated to the pathologist so that the predictions made from the biopsy can be confirmed or corrected if possible. Renal allograft biopsy interpretation is therefore developed out of a discussion between clinician and pathologist and is a learning process for both based on the 'patient's clinical course.
[Table:I], shows the indications for biopsy i.e. the clinical question about 78 consecutive cases. The questions were as follows: Why has this patient developed acute renal failure? Why has this patient developed protoinuria? And most often, why is this progressive decrease in graft function occurring inspite of adequate and increased Immunosuppression, and after establishing that the graft anastomoses - arterial, venous and ureteric are all functioning adequately, and that no other serious complication such as graft infection is present. The decreasing renal function may be combined with proteinuria. The specimen that the pathologist receives has, as it were, been passed through a ‘filter’ that has already eliminated some of the possible answers to the clinical question.
The pathological changes observed in these biopsies are shown in the [Table - 1].
The following diagnoses wore made: acute cellular rejection, acute vascular rejection, chronic vascular rejection, transplant glomerulopathy, glomerulonephritis, cortical necrosis and one case each of acute tubular necrosis, oxalosis and cyclosporine toxicity. It is noteworthy that biopsies from five grafts with decreasing renal function showed no abnormality on light microscopy, a reminder that though generally representative of the kidney as a whole, a biopsy sample may not be so, and vascular rejection in particular shows much variation in severity from one vascular segment to the next, even in a single biopsy. It will be seen in [Table - 1] that the number of diagnoses is in excess of the number of the cases.
This is because small areas of acute cellular rejection often accompany other lesions and some conditions such as vascular rejection and transplant glomerulopathy frequently go together.
[Table:II] has sorted out the excess by separating possibly less important diagnoses, from the main causes of the clinical findings observed. This is arrived at by clinical correlation.
The presence of areas of cortical necrosis in seven biopsies requires some comment. The two cases presenting with acute renal failure appeared to be the end result of an accelerated acute vascular rejection with vascular obstruction causing tissue necrosis. In the five cases presenting with gradually diminishing renal function a variety of processes including, arterial injury or tying off of small vessels during surgery, kinking of the renal vein, perfusion damage to endothelium, infection etc., could have resulted in the loss of a critical amount of renal parenchyma of sufficient magnitude to decrease renal function and result in progressive loss of surviving nephrons. Proteinuria in most cases was associated with either de novo or recurrent glomerulonephritis or transplant glomerulopathy. Decreasing renal function in the majority of cases was the result of vascular rejection or transplant glomerulopathy.
Immunofluorescence studies had been done on all the biopsies, but most pathologists would agree that they are of limited value except when proteinuria is present. In this situation it assists in the classification of any glomerulonephritis detected and helps to distinguish glomerulonephritis from transplant glomerulopallthy, which usually shows only unpatterned, weak and variable staining with the reagents.
The increasing use of cyclosporine A is often perceived as a problem by the pathologist, because of the felt obligation to diagnose toxicity relying upon morphological changes such as interstitial congestion, diffuse interstitial fibrosis, isometric cytoplasmic, vacuolation and inclusion in tubules, striped fibrosis, and acute arteriolopathy. These lesions are in the main of low sensitivity and specificity - being absent in many cases of cyclosporine toxicity or being so non-specific as to provide no firm foundation for diagnosis. In point of fact, this is seldom a problem in our country, where low doses of cyclosporine are used in combination with other immunosuppresive agents, and usually for a short duration, because of the high costs involved. In cases where a diagnosis of cyclosporine-toxicity is seriously being considered by the clinician, it is often tested by decreasing the dose and waiting for a corresponding improvement in renal function. The presence of changes attributable to cyclosporine toxicity, when noticed in the biopsy, should be recorded, and the possibility of toxicity discussed with the clinician.
Most of the diagnoses listed in the table have no specific treatment. However, this information is important in patient management, providing as it does, a basis for prognostication and for counselling the patient and his family.
The data presented is from material contained in an unpublished Madras University, MD Pathology dissertation by Dr. Isha Bishnoi- now Garg, and now of the Department of Pathology, St. John's Medical College, Bangalore.
[Table - 1], [Table - 2]