What is your approach to immunosuppression in patients with preserved kidney function who are found to have nephrotic syndrome of unknown etiology and cannot safely undergo a kidney biopsy?
In patients with preserved kidney function who have nephrotic syndrome of unknown etiology and cannot safely undergo a kidney biopsy, what steps would you consider in your approach to management?
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This is a difficult scenario. Would definitely try to get a biopsy at a Higher level of care perhaps by Interventional Nephrology.
Would obtain a comprehensive laboratory workup including kidney function, serum albumin level, random and 24-hour urine collection for albuminuria and proteinuria, Hepatitis B and C, HIV, ANA, ds-DNA, syphilis testing, PR-3, MPO, Anti-GBM titer, SPEP/SIFE/UPEP/UIFE, and membranous serum panel [for PLA2R and THSD7A], A1c, Lipid panel, PT/PTT/INR, APLS testing [if warranted]. Would carefully make sure to look at the medications patient is on esp. NSAIDs, supplements including Lipoic acid use, skin cream [laced with mercury sometimes]. Lipoic acid and mercury skin creams are usually associated with NELL-1 membranous nephropathy wherein patients respond by removal of the offending agents and immunosuppression is not likely warranted. Regardless, in cases medication offenders particularly NSAIDs need to be held.
If kidney function is preserved and there is no diabetes and secondary membranous nephropathy etiology screening is negative but serum PLA2R titer is significantly high [> 50 RU/mL] and patient has proteinuria > 3.5 grams/day and severely hypoalbuminemic, would treat with immunosuppression preferably rituximab and monitor clinical parameters and lab parameters including PLA2R titers.
If kidney function is preserved and patient is floridly nephrotic with absence of diabetes and normal/low BP, elevated lipid panel, and urine albuminuria divided by urine proteinuria > 90% --> this is more suggestive of minimal change disease [MCD] and would treat empirically for MCD with high dose glucocorticoids >> CNI/Rituximab. Usually, nephrosis will improve within 4 weeks.
If kidney function is not preserved, and cannot obtain a kidney biopsy, and patient is floridly nephrotic with absence of diabetes but has elevated serum creatinine and has hypertension, and elevated lipid panel --> would favor primary FSGS and would treat empirically for MCD with high dose glucocorticoids >> CNI/Rituximab. In this scenario, it may take at least 8-12 weeks to assess the effects of treatment. If there is no response, this may be steroid-resistant, and a targeted gene panel of blood should be obtained. If this scenario is suspicious for a genetic FSGS, more family history needs to be taken; treatment in this case would be a CNI.
If there is concomitant hematuria but preserved kidney function, MCD, primary FSGS and primary >> secondary membranous etiologies are possible. Also this could be a lupus podocytopathy in select patients. IgA Nephropathy (+) Podocytopathy is also possible.
Would make sure that there is no evidence of systemic malignancy by performing age appropriate cancer screening. Certain conditions like lymphoma and IgG4 nephropathy are associated with glomerular diseases including podocytopathy and membranous nephropathy and if these can be diagnosed and treated [along with systemic glucocorticoids], clinical responsiveness of nephrosis can be seen.
In all cases, conservative management is paramount - ACEi/ARB, diuretics, BP control, control of blood sugars/lipids, weight loss. If patient responds with conservative management +/- immunosuppression, clinical surveillance is warranted.