#198 Different patterns of renal thrombotic microangiopathy
Authors: Guasch Anna Domínguez , Arce Yolanda , Bachouti Jonas E l , Tinoco Adria , Pasache Hans Kevin , Basantes Andrea Catalina , Marco Helena , Torra Roser , Guirado Lluis , Encarnacion Montserrat Mercedes Diaz , Barros Xoana 
Published: May 2024

Abstract

Background and Aims
Thrombotic microangiopathy (TMA) is a renal lesion often associated with microangiopathic hemolysis. However, there are cases of TMA that present without hemolysis, hematuria or even proteinuria, sometimes being an incidental histopathological finding. In these situations, little is known about the long-term effects on renal function.
The aim of our study is to describe the clinical and histopathological presentation of patients with renal TMA biopsied in our center, focusing on those without hemolysis and with low clinical suspicion of TMA.

Method
We conducted a retrospective observational unicentric study. Clinical and histological parameters were collected from patients biopsied between 2015 and 2023, whose renal biopsy (RB) showed TMA, with a minimum follow-up of 6 months. We excluded renal transplant recipients.

Results
Data were collected from 41 patients (17 men, 24 women), with a mean age at the time of RB of 54 ± 16 years and a mean eGFR of 80 ± 23 ml/min/1.72 m2. 12 of them (29%) had chronic kidney disease (CKD).
Twenty-seven patients (66%) did not have hemolysis at diagnosis. Compared to patients with hemolysis, they were of older age (58 vs 47 years, p = 0.030) and had higher prevalence of CKD (41% vs 7%, p = 0.028). They had a milder clinical presentation, with lower creatinine (168 vs 419 μmol/L, p = 0.029), lower need for renal replacement therapy (RRT) (4% vs 50%, p = 0.001), less hematuria (33% vs 79%, p = 0.008) and proteinuria (67% vs 100%, p = 0.035). Histologically, patients without hemolysis had less fibrosis (56% vs 86%, p = 0.084) and fewer chronic TMA lesions (double contours, wrinkling of the basement membrane) (52% vs 93%, p = 0.009), despite delayed renal biopsy compared to patients with hemolysis (99 ± 118 vs 28 ± 30 days since clinical presentation, p = 0.036). The causes of TMA that were most commonly associated with the absence of hemolysis were drugs (89% without hemolysis) and glomerulopathies such as IgA nephropathy, minimal change disease and fibrillary glomerulonephritis (100% without hemolysis).
Within this group of patients without hemolysis, 13 (32%) had a low clinical suspicion of TMA, defined as the absence of hemolysis, hypertension and predisposing factors, in some cases being an incidental finding in the RB. As expected, they also had a mild presentation and did not require RRT. In some cases, they even presented without proteinuria (7 patients, 64%). When comparing the severity of the lesions in renal tissue with patients with high clinical suspicion of TMA, patients with low clinical suspicion presented a similar prevalence of mesangiolysis, vascular damage and a similar proportion of affected glomeruli. Chronic TMA lesions were present in both groups (Table 1).
When analysing the evolution of renal function, there are several confounding factors to consider (higher prevalence of CKD in patients without hemolysis, targeted treatment in patients with hemolysis, different time of follow-up between groups...). In our results, there were no statistically significant differences in the evolution of creatinine and proteinuria between groups, even when TMA was an incidental finding. In our sample, these findings were not attributable to a larger number of other histopathological lesions in patients with low suspicion of TMA, as there were no differences between groups (see Table 1).

Conclusion
Renal TMA should be suspected even in the absence of hemolysis, hypertension or proteinuria, as in our sample one third of diagnoses were incidental and their mild presentation may have delayed renal biopsy.
The severity of histological lesions and the evolution of renal function in these cases are comparable to those of patients with a high clinical suspicion. Therefore, its prompt identification, etiological study and treatment are equally important.
Currently, we have insufficient data to provide the different clinical scenarios in which TMA should be suspected. However, based on our findings, in the presence of drugs TMA should be considered in the differential diagnosis along with Acute Interstitial Nephritis, even in the absence of urinary abnormalities.