Saudi Journal of Kidney Diseases and Transplantation

CASE REPORT
Year
: 2019  |  Volume : 30  |  Issue : 1  |  Page : 221--225

IgA nephropathy: Missed diagnosis and renal transplant


Abeer Shaker Al-Moursy Ali1, Nasir A Al-Subai2, Ahmed Y Shebly2, Hatem Q Al-Maghraby3, Wesam Ahmed Nasif4,  
1 Department of Pathology, Faculty of Medicine, Umm Al-Qurra University, Mecca, Saudi Arabia
2 Medical Student, Faculty of Medicine, Umm Al-Qurra University, Mecca, Saudi Arabia
3 Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia
4 Department of Biochemistry, Faculty of Medicine, Umm Al-Qurra University, Mecca, Saudi Arabia

Correspondence Address:
Wesam Ahmed Nasif
Department of Biochemistry, Faculty of Medicine, Umm Al-Qurra University, Mecca
Saudi Arabia

Abstract

The most common form of chronic glomerulonephritis worldwide is IgA nephropathy (IgAN) where IgA immune complexes are deposited in the glomeruli. About 40%–45% of patients with IgAN present with macroscopic hematuria. Diagnosis occurs through kidney biopsy to visualize IgA deposition in the glomerular mesangial area using immunofluorescence microscopy. We presented a 21-year-old patient referred to the nephrology department for follow-up after renal transplantation. His condition started at the age of nine-year with macroscopic hematuria. At the age of 14 years, he presented with hematuria and serum creatinine of 62 umol/L and was diagnosed with acute cystitis. At the age of 18 years, the patient was admitted with generalized fatigue, muscle cramps, and gross hematuria. Kidney biopsy showed advanced glomerulosclerorosis and IgAN with mesangial hypercellularity. The patient was started on peritoneal dialysis for four months following which he underwent kidney transplant from a nonrelative living donor.



How to cite this article:
Al-Moursy Ali AS, Al-Subai NA, Shebly AY, Al-Maghraby HQ, Nasif WA. IgA nephropathy: Missed diagnosis and renal transplant.Saudi J Kidney Dis Transpl 2019;30:221-225


How to cite this URL:
Al-Moursy Ali AS, Al-Subai NA, Shebly AY, Al-Maghraby HQ, Nasif WA. IgA nephropathy: Missed diagnosis and renal transplant. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Aug 19 ];30:221-225
Available from: http://www.sjkdt.org/text.asp?2019/30/1/221/252914


Full Text



 Introduction



IgA nephropathy (IgAN) which was first reported by Berger et al in 1968 is the most common form of chronic glomerulonephritis worldwide. It is characterized by the presence of predominant IgA deposits in the glomerular mesangium.[1] Although considered as a benign condition with favorable outcome, it might progress to end-stage renal disease (ESRD). All age-groups can be affected with IgAN, but it is mainly present in patients in the age-group 10–30 years, more predominant in males, with a male-to-female gender ratio of 2:1.[2] About 40%–45% of patients with IgAN present with macroscopic hematuria, in addition to microscopic hematuria and 35%–40% with proteinuria rarely present with nephritic syndrome or acute renal failure.[1] Diagnosis is made through kidney biopsy to visualize IgA deposition in the glomerular mesangial area using immunofluorescence microscopy.[3] There are no clearly identified etiology and pathophysiology of IgAN, but evidence suggests an interaction between various genetic and environmental factors.[4] We report a case of a 21-year-old Saudi male with crescentic IgAN whose condition progressed to ESRD and underwent a renal transplant at the age of 18 years due to misdiagnosis.

 Case Report



A 21-year-old Saudi medical student was referred to the Nephrology Department for follow-up after renal transplantation. With full past medical and surgical history, we noted that at the age of nine years, his parents sent him to the pediatrician because of macroscopic hematuria at the end of urination which was accompanied with burning sensation during urination. Urethral dilatation was performed without any explanation for the reason of this intervention. At the age of 14 years, the patient's parents referred him to their general physician with blood in the last drip of urine wetting his clothes; the blood was small in quantity; general and systemic examination revealed no significant findings, he was afebrile with normal blood pressure. In spite of that, he was diagnosed with having cystitis. Laboratory tests were performed; urine culture revealed no growth and kidney function tests including serum creatinine was 62 umol/L (reference range: 40–90). Treatment with antibiotic in the form of Augmentin (amoxicillin clavulanate) 652 mg tablet was instituted. At the age of 15 years, the symptoms recurred. Ultrasound of the kidney and bladder was recommended with no significant findings. Laboratory test in the form of urine culture and urinalysis was performed, and he was diagnosed to have urinary tract infection and treated with Bactrim (sulfamethoxazole and trimethoprim) 480 mg tablet twice daily for seven days. The condition continued to wax and wane till the age of 18 years; the patient came to the emergency room complaining of nausea, vomiting, and diarrhea of three weeks duration, generalized fatigue and muscle cramping for 1½ months and sometimes gross hematuria in the last drop of urine. He was admitted to the hospital. Full physical and general examination indicated high blood pressure. He had bilateral minimal lower limb edema. He was conscious, well oriented, not confused. Body mass index was 44.8 kg/m2 (his body weight was 106.5 kg and height was 156 cm). Laboratory tests showed the following: hemoglobin, 7.0 g/dL; platelets, 370 × 109/L; blood urea, 41.6 mmol/L; creatinine, 1034 μmol/L; sodium 137 μmol/L; total protein, 71g/L; albumin, 33 g/dL; total bilirubin 4.7 μmol/L; aspartate aminotransferase 22 IU/L and, alanine aminotransferase: 75 μmol/L. Chest radiography was normal. Ultrasono-graphy of the abdomen and pelvis revealed that both kidneys showed increased echo-genicity with no hydronephrosis or renal calculi. Right kidney measured 10.0 cm × 4.33 cm × 1.18 cm and, left kidney measured 10.5 cm × 5.04 cm × 1.8 cm. Renal biopsy was performed. On light microscopic examination, advanced glomerulosclerosis and features suggestive of IgAN with mesangial hyper cellularity and crescents were present along with severe interstitial fibrosis and tubular atrophy and mild hyaline arterial sclerosis [Figure 1]a and [Figure 1]b. Immunofluorescence microscopy [Figure 2] showed granular mesangial deposits of IgA, C3 and Kappa and Lambda. IgM, IgG and C1Q, fibrinogen and albumin were negative.{Figure 1}{Figure 2}

Treatment was initiated initially with intravenous steroids. Later, he had workup done for the hemolytic uremic syndrome, thrombocytopenic purpura (HUS/TTP) and rapidly progressive glomerulonephritis (RPGN), which were ruled out. Autoimmune disease workup was negative; anti-nuclear antibody: 0.35, complement T3: 1.44, c-antineutrophil cytoplasmic antibodies (ANCA): 0.78 and pANCA: 1.44. Hemodialysis (HD) was begun three times per week for one month to eliminate the risk of uremic bleeding from platelet dysfunction. He was given one unit of packed red blood cells in the emergency room. Initially, his blood pressure was high, and he was started on dual antihypertensives, and it was controlled before his kidney biopsy. Kidney biopsy showed ESRD with advanced glomerulosclerosis. The patient and his parents were counseled regarding dialysis and they preferred peritoneal dialysis (PD) for four months, following which he underwent kidney transplant from a nonrelative living donor. At this stage, the patient's condition was stable on: tacrolimus 1 mg (prograf) twice per day, mycophenolate mofetil 500 mg tablet (cellcept) twice per day, prednisolone 5 mg once per day, asprin 81 mg once per day and now his creatinine level is stable at 134 at last follow-up.

 Discussion



IgAN is the most widely recognized glomerulonephritis and rapid progression to ESRD is uncommon (<10%).[5] Substantial evidence suggests that it is an immune-mediated disease in which circulating IgA immune complexes are deposited in the glomeruli. It is well known that a genetically determined increase in circulating levels of IgA1 with galactose-deficient O-glycans in the hinge-region (Hit 1) is determined in patients with IgAN. Renal injury is not attributed to this glycosylation aberrancy. At the same time, synthesis and binding of antibodies directed against galactose-deficient IgA1 are required for the formation of immune complexes that accumulate in the glomerular mesangium (Hits 2 and 3). Immune complexes activate mesangial cells, inducing proliferation and secretion of extracellular matrix, cytokines, and chemokines, which result in renal injury (Hit 4). Elucidation of the pathogenesis of IgAN provides an opportunity to develop disease-specific therapies.[6]

Diagnosis of IgAN mostly occurs in the second or third decades of life. Reported male: female ratios range from 2:1 to 6:1.[2] Although IgAN is primarily characterized by mesangial IgA deposition, light microscopic appearances, and clinical features of patients can vary considerably. Proliferative and crescentic forms of IgAN are associated with nephrotic-range proteinuria. About 25%–30% of patients accordingly require renal replacement therapy within 20–25 years.[2] Hypertension, severity of proteinuria, and the presence of severe lesions on initial renal biopsy such as hyalinosis and crescents are the most predictive factors for progression to ESRD.[1] Here, we pooled the clinical and pathological findings of this patient which started at the age of nine years with macroscopic hematuria and burning micturition; several studies of IgAN in children have shown that >80% of all patients have microscopic hematuria. Indeed, recurrent macroscopic hematuria has conventionally been considered the hallmark of childhood IgAN.[7] The case was diagnosed with cystitis in spite of the patient being afebrile with urine culture that revealed no growth and kidney function tests, including serum creatinine was 62 umol/L. Several years later, the condition deteriorated as the patient presented to the emergency department with evidence of ESRD. The patient's renal biopsy on light micros-copic examination showed advanced glomeruloscelorosis and features suggestive of IgAN with mesangial hyper cellularity and crescents along with severe interstitial fibrosis and tubular atrophy with mild hyaline arterial sclerosis. It is well known that multidiscipline treatment therapy for such cases is optional according to the case and pathological findings; steroid therapy was the initial therapy followed by HD three times per week for one month to eliminate the risk of uremic bleeding from platelet dysfunction. Linné reported a patient who presented with SCr >16 mg/dL, BUN of 182, with rapidly progressive clinical course and positive serology for ANCA. With pulse steroids and immunomodulation, the patient needed long-term dialysis.[8] It was found that patients with crescentic IgAN had a poor prognosis, and nearly 70% of these patients progressed to ESRD in five years, including those patients who had received immuno-suppressive therapy. Patients with early-stage disease had a good prognosis, with <25% of patients progressing to ESRD during follow-up.[9] Our patient and his parents thought that renal transplantation is more helpful to the condition than either HD or PD.

To our knowledge, treatment of IgAN is still uncertain, other than the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for blood pressure control and proteinuria. At the same time, the use of glucocorticoids alone or in combination with other immunosuppressive drugs may result in stabilization of renal function in approximately 50% of patients with IgAN at high-risk for the progression of renal disease. More importantly, a decrease in proteinuria of 50% or more within six months predicted a sustained response to therapy.[8]

Peters et al in 2015 reported that immunosuppressive therapy seems to benefit only a subset of high-risk patients with IgAN. It also seems that currently it is impossible to identify this sub-group using clinical or pathological characteristics. Considering this, their finding that a 50% decrease in proteinuria within six months after the start of therapy is indicative of a sustained response to immunosuppressive therapy and is highly relevant.[10] In patients lacking a substantial decrease in proteinuria after six months of therapy, discontinuation of treatment should be strongly considered, in our opinion.

For cases of idiopathic crescentic glomerulo-nephritis, the recommended treatment consists of intravenous pulse methylprednisolone followed by oral prednisone, intravenous or oral cyclophosphamide, eculizumab (the complement factor 5 inhibitor) and/or plasmapheresis.[10],[11],[12] This recommendation was the treatment option for aHUS include plasma exchange and, eculizumab. Some investigators have reported that eculizumab is more effective in the early treatment of aHUS as it can protect the kidneys from ongoing complement-mediated damage and to allow the kidneys to recover from the reversible changes.[13],[14]

In this case report, we present an overview of a case with advanced glomerulosclerosis and features suggestive of IgAN with mesangial hypercellularity and crescents. The patient had many poor prognostic factors including male gender, nephrotic proteinuria, renal impairment, and severe macroscopic findings. In addition to these bad prognostic factors the patient was misdiagnosed as cystitis from the age of nine years; hence, in spite of starting steroid therapy, later on, the condition showed the deterioration of renal function which was caused by aberrantly glycosylated serum IgA1, which causes mesangial IgA deposition and inflammatory changes, such as crescent formation and endothelial hypercellularity in the glomeruli. Subsequently, since the patient presented with HUS/TTP and RPGN at the age of 14 years and ESRD, there were no other options to treat the patient except renal transplant which is the treatment of choice for individuals with progressive renal failure due to IgAN.

 Conclusion



The case described in this report is an unusual missed case in that the child had IgAN associated with rapid deterioration of kidney function and nonresponsiveness to steroid therapy. This rare combination of disorders was successfully treated with renal transplant.

Conflict of interest:

None declared.

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