In 1985, researchers described C1q nephropathy (C1qN). The condition is characterized by (1) the presence of predominant or co-dominant mesangial C1q deposits detected by immunofluorescence microscopy; (2) corresponding mesangial or paramesangial electron-dense deposit (EDD); and (3) absence of clinical and serological evidence of systemic lupus erythematosus (SLE). Patients present with proteinuria in the nephrotic range and are resistant to steroid treatment.
Previous studies have revealed the clinical heterogeneity of C1qN, with some cases having normal urinalysis results. Takahiro Kanai, MD, PhD, and colleagues recently conducted a long-term observational study designed to confirm the existence of cases with predominant mesangial C1q deposits and negative or mild proteinuria and/or hematuria. The researchers examined renal graft biopsy specimens demonstrating negative to mild proteinuria, defined as ≤1+ by dip stick test, and/or hematuria, defined as ≤1+ by dip stick test. Results of the study were reported online in BMC Nephrology [doi.org/10.1186/s12882-018-0874-9].
The study included 414 serial cases with negative to mild proteinuria and/or hematuria who underwent renal transplantation. Specimens of renal graft biopsy were obtained from the Kidney Center in Tokyo Women’s Medical University between 2002 and 2005. Cases included 334 adults >19 years of age and 80 pediatric patients two to ≤18 years of age. Of the total cohort, 242 were male and 172 were female.
Eligibility criteria included predominant mesangial C1q deposits 2+ or greater on a ±4 scale by the definition of C1q deposits, and a follow-up period of >10 years after detection of the predominant C1q deposits in the mesangium. Exclusion criteria included morphologic features of membranoproliferative glomerulonephritis type 1 or fulfillment of the diagnostic criteria for SLE due to mesangial C1q deposits.
Patient medical records were reviewed, including notation of the age at detection of predominant mesangial C1q deposits, sex, original renal disease, reason for the renal graft biopsy, and blood pressure levels. The review also included results from laboratory tests, including degree of proteinuria and hematuria, anti-C1q antibody titers, and serum creatinine levels. Medication data were also collected, including use of steroids, immunosuppressants, angiotensin receptor blockers (ARBs), and angiotensin converting enzyme (ACE) inhibitors.
At study selection, five pediatric patients (male to female ratio, 1:1.5) met the criteria for C1qN. The samples from those five patients represented 0.01% of all samples studied. Original renal diseases of the five patients were renal hypoplasia, focal segmental glomerulosclerosis, autosomal recessive polycystic kidney disease, Alport syndrome, and chronic tubulointerstitial nephritis. Mean age at time of renal transplantation was 8.8 years.
Reasons for renal graft biopsy when predominant C1q deposits were detected were due to protocol in four cases and mild proteinuria in one case. Protocol renal graft biopsies were conducted an average of 2.2 times (range, 1-3 times) prior to detection of predominant mesangial C1q deposits. None of the five cases presented with hypertension or signs or symptoms of infection at the time of detection of predominant mesangial C1q deposits. Following detection of predominant mesangial C1q deposits, follow-up ranged from 10 to 11 years.
At the time of detection of predominant mesangial C1q deposits, two cases presented with mild proteinuria (1+ by dip stick tests) without hematuria. The remaining three cases had normal results to urinalysis.
Anti-C1q antibody titers were in the normal range for all five cases. Four of the cases had normal serum creatinine levels and stable renal function. One patient had a moderate increase in serum creatinine levels, from 0.5 to 1.2 mg/dL, due to acute rejection. The patient maintained stable renal function after that. None of the patients presented with persistent proteinuria and/or hematuria ≥2+ by dip stick test, and no cases presented with hypertension or developed SLE.
The immunosuppressive agents the five patients were given included tacrolimus hydrate (adjusted to target level of 3-5 ng/mL, (mycophenolate mofetil (700 mg/m2/day), and methylprednisolone (1-4 mg/day).
Two of the patients had received an ARB (losartan potassium at 100 mg/day or 25 mg/day) at the time of diagnosis. All patients had received ARBs 10 years after the predominant C1q deposits were detected. None of the patients had received ACE inhibitors at time of detection of predominant C1q deposits or 10 years later.
Light microscopy revealed averages of 28 glomeruli, all of which showed minor glomerular abnormalities. Immunofluorescence microscopy revealed predominant mesangial C1q deposits and co-deposits. With the exception of one case whose specimen also exhibited staining in some capillary loops, Cq1 deposits were limited to the mesangium or para-mesangium areas. Only one case showed IgA deposits.
All selected specimens showed EDDs in the mesangium on electron microscopy. One case had subendothelial deposits and two cases had subepithelial deposits. None of the cases showed tubuloreticular inclusions or foot process effacements.
“This long-term observational study on transplanted kidneys confirms that there are cases with predominant but silent C1q deposits in the mesangium who have negative or only mild proteinuria with minor glomerular abnormality. This provides a first step towards a better understanding of the role of predominant mesangial C1q deposits,” the researchers said.
- Researchers studied renal graft biopsy specimens with negative to mild proteinuria and/or hematuria to confirm the existence of cases of predominant mesangial C1q deposits in that patient population.
- Five pediatric patients (male to female ratio, 1:1.15) met inclusion criteria. The samples from the included cases represented 0.01% of all samples investigated.
- The study results confirmed the existence of cases with predominant but silent C1q deposits in the mesangium who have negative to mild proteinuria.