Indian Journal of Transplantation

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Year
: 2021  |  Volume : 15  |  Issue : 3  |  Page : 282--283

Chronic allograft nephropathy with proteinuria


Praveen Kumar Etta1, Thatipamula Madhavi2,  
1 Department of Nephrology and Kidney Transplantation, Virinchi Hospitals, Hyderabad, Telangana, India
2 Department of Radiodiagnosis, Niloufer Hospital, Hyderabad, Telangana, India

Correspondence Address:
Dr. Praveen Kumar Etta
Department of Nephrology and Kidney Transplantation, Virinchi Hospitals and Max Superspeciality Medical Centre, Hyderabad - 500 034, Telangana
India




How to cite this article:
Etta PK, Madhavi T. Chronic allograft nephropathy with proteinuria.Indian J Transplant 2021;15:282-283


How to cite this URL:
Etta PK, Madhavi T. Chronic allograft nephropathy with proteinuria. Indian J Transplant [serial online] 2021 [cited 2022 Dec 7 ];15:282-283
Available from: https://www.ijtonline.in/text.asp?2021/15/3/282/327397


Full Text

 History and Examination



A 56-year-old kidney transplant (KT) recipient with hypertension from 16 years presented 6 years after KT, with gradually progressive graft dysfunction and proteinuria from 6 months. His native kidney disease (NKD) was presumed as chronic glomerulonephritis (GN). Dialysis vintage before KT was 5 months. Human leukocyte antigen (HLA) mismatch was 2/6 (donor was brother). He did not receive induction and was taking the standard triple-drug immunosuppression with near-normal graft function till 6 months ago. He was diagnosed with pulmonary tuberculosis at 6 months after KT and was started on modified antituberculosis therapy (ATT). However, the patient was noncompliant and ATT was prematurely terminated after 2 months due to intolerance. He was lost to follow-up till 3 months ago when he presented with low-grade fever, malaise, and edema of lower limbs with weight gain of around 8 kilograms. General examination revealed significant edema and pallor. Chest examination revealed coarse crackles at the right upper zone with no obvious tracheal deviation. Other systems were normal, except for nonfunctioning arteriovenous fistula in the left forearm. There was no tenderness at graft site.

 Differential Diagnosis



The differentials thought at this point are

Chronic rejection: The patient might have missed immunosuppression in the background of noncompliance and infrequent follow-ups. Significant edema with proteinuria and delayed presentation favors chronic antibody-mediated rejection (ABMR) with transplant glomerulopathy (TG) as the first possibilityDe novo GN: Delayed presentation with significant edema favors the possibility of de novo GN, especially de novo membranous nephropathy, which is the most common form of de novo GN following KTRecurrence of primary GN: It usually presents within 3 years following KT, but can present later also. Hypertension with chronic GN from 40 years of age which progressed to end-stage kidney disease (ESKD) over the next 10 years may favor chronic IgA nephropathy (IgAN) as the underlying NKD. IgAN is also the most common primary glomerular disease worldwide. Histological recurrence can be seen in >50% (protocol biopsies) and can lead to graft loss in 20%–30%Chronic calcineurin inhibitor toxicity: It is one of the most common causes of chronic allograft nephropathy (CAN). Significant edema with proteinuria is uncommonViral nephropathies: Patients with excessive immunosuppression might develop viral infections such as BK virus nephropathy. As the index patient was not on regular follow-ups with infrequent therapeutic drug monitoring, this can be a possibility, though significant proteinuria is unusualGranulomatous interstitial nephritis (GIN): In the background of untreated tuberculosis, GIN can be another rare possibility.

 Laboratory Evaluation



His laboratory investigations revealed a creeping rise in creatinine level over 5 months (2.1–3.7 and then to 4.6 mg/dl) with significant proteinuria. Complete urine examination showed 3+ albumin with 6–8 red blood cells per high power field. Spot urine protein to creatinine ratio was 3.2 g/g. Serum albumin was 2.8 g/dl. Tacrolimus trough level was 3.1 ng/ml. HLA donor-specific antibody assay was not done. Ultrasound and Doppler showed increased echogenicity of the graft with raised resistive index. These reports favored the possibility of chronic ABMR with TG.

Allograft biopsy was performed.

Light microscopy revealed 50% sclerosed glomeruli; viable glomeruli showed prominent eosinophilic, periodic acid-Schiff (PAS) negative, silver negative deposits in the mesangium, and walls of the blood vessels. The underlying tuft showed mesangial hypercellularity. Moderate-to-severe interstitial fibrosis (40%–50%) was noted [Figure 1]. Most of the glomerular deposition diseases such as monoclonal immunoglobulin deposition disease, fibrillary, and immunotactoid glomerulopathies show PAS-positive and silver-negative deposits. Only amyloid and collagenofibrotic glomerulopathies show both PAS and silver-negative deposits. On further evaluation, the deposits were congophilic with apple-green birefringence on a polarized microscope confirming it as amyloid. Immunofluorescence study showed significant mesangial deposits of IgA with IgG and C3c. The deposits did not show light chain restriction. Immunohistochemistry for AA amyloid was done and it was positive [Figure 1]. C4d staining was negative. Renal biopsy showed features of combined IgAN and AA amyloidosis. The cause for de novo secondary amyloidosis of allograft is probably the underlying untreated tuberculosis. He was restarted on modified ATT (without rifampicin) after chest imaging and sputum studies. He was also evaluated for other systemic effects of amyloidosis. IgA deposits probably represent the recurrence of primary IgAN in the allograft.{Figure 1}

Teaching points:

CAN with significant proteinuria most commonly results from either chronic rejection (chronic ABMR) or GN (de novo or recurrent)The possibility of secondary amyloidosis should be kept in mind in patients with chronic infections and inflammatory disorders.[1] Rarely, it can also result secondary to chronic rejection and neoplasms [Table 1]Renal involvement is seen in the majority (>90%) of patients with secondary amyloidosis and can lead to ESKD or graft loss.[2],[3]{Table 1}

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Harrison KL, Alpers CE, Davis CL. De novo amyloidosis in a renal allograft: A case report and review of the literature. Am J Kidney Dis 1993;22:468-76.
2Rojas R, Josephson MA, Chang A, Meehan SM. AA amyloidosis in the renal allograft: A report of two cases and review of the literature. Clin Kidney J 2012;5:146-9.
3Yılmaz S, Özçakar ZB, Bulum B, Kiremitçi S, Ensari A, Ekim M, et al. De novo amyloidosis in a renal transplant patient. Pediatr Transplant 2014;18:E259-61.