Consult Rounds: Cryoglobulins and paraproteinemias

What is the connection of cyroglobulins(cyro) with paraproteinemias or myelomas?

Cryoglobulins are Igs that reversibly precipitate at temperatures <37°C. The precipitation results in symptoms that are seen in vasculitis: rash, ischemia, ulcers, joint pains, fatigue, and glomerulonephritis. The pathogenesis of cryoglobulin-induced injury involves two main mechanisms, hyperviscosity and immune complex deposition, that activate complement and induce vascular inflammation. Classically, in the renal community, we see this in Hep C association and other infections. In the “Harvoni” era of Hep C treatment, cyro associated MPGN from Hep C is likely on a downtrend.

What about with paraproteinemias?

In the largest case series of type 1 cryoglobulinemia associated with MM, six of seven patients were men 28–69 years of age, and all had stage 1 indolent myeloma. Three patients had an IgGκ monoclonal protein, three had an IgGλ monoclonal protein, and one had an IgMλ monoclonal protein. Skin changes and rheumatologic failure were the most common presenting symptoms. Renal manifestations were reported in two patients who presented with nephrotic syndrome and AKI.

Pathology usually shows an MPGN pattern of injury on LM and hyaline thrombi within glomerular capillaries. IF may reveal staining for various Igs within hyaline thrombi and the subendothelial space, and monoclonal light chain restriction may be observed in types 1 and 2 cryoglobulinemia. On EM, cryoglobulins may appear as paired, curved microtubules with a diameter of 20–30 nm), although it should be noted that this feature is observed in only a subset of patients.

In patients with cryoglobulinemia associated with a lymphoproliferative disorder, treatment should focus on the underlying hematologic malignancy that is producing the cryoglobulin. Fludarabine- and rituximab-based regimens have been used to treat type 1 cryoglobulinemia associated with MGUS, Waldenstrom macroglobulinemia(WM), and NHL. Antimyeloma therapies, including bortezomib, thalidomide, and lenalidomide, have shown efficacy in the treatment of type 1 cryoglobulinemia associated with MM.  With WM, besides AL amyloidosis, cyro MPGN is commonly seen as the GN manifestation.

High index of suspicion is required to connect the dots and many times the bone marrow and testing might be negative. As we have learnt, the clone might not be that large but it is noxious to the kidney.

Check out this recent CJASN review from few years ago on Paraprotein associated GNs

Kidneys Rule the world!- Let's create some Kidney Madness

World Kidney Day is celebrated to acknowledge all who are suffering from kidney disease and to all kidney professionals who take care of patients with kidney disease.

Every year, I write about why Nephrology is the best field in medicine during kidney month. It’s my favorite month- as it’s my birthday month, coming of Spring, and showcases our profession of Nephrology. 

While Nephrology may be facing challenges in recruiting, there is a lot of deep medicine in what we practice in nephrology.  As Eric Topol says in his recent book, "most of us are practicing shallow medicine".  In other words, we fall for the quick cook book algorithms and screenings and are avoiding the personalized medicine. I think as a field, Nephrology allows for a more deeper form of medicine. Given lack of many randomized trials, we rely on our experience, patho-physiology and clinical acumen a fair amount and this takes us away from cook book medicine.  

How does one treat a C3 glomerulonephritis? The recent KDIGO2019 update tried to shed some light on that but basically we borrowed our treatment from other glomerular diseases and then we used patho-physiology based strategy of inhibiting the complement cascade since it’s a complement disorder.

It's not just the science....what is also exciting about Nephrology is that we are the front-runners in adopting social media in it’s education and spreading of knowledge. Other fields in medicine followed but thanks to some great strides made early on, we achieved this as a field. AJKD is probably one of the first few sub-specialty journals to have it’s own blog. 

Finally, we all love to have fun. Go out there this month and join and create some renal madness. Oh sorry, we cannot say renal- shall we change all renal to kidney ( as most journals want us to) or should be say NephMadness!!. Yes, we also are the pioneers in creating games in medicine.

What else can you ask for from your doctor- detail oriented, compassionate, smart( extremely), most well dressed in the hospital, have one of the least burn out rates, make decent money, are social media friendly and make good leaders( med directors in dialysis units). 

In addition, for the science lovers, nephrologist also are good scientists and willing to publish both positive and negative trials in medicine( a balanced fluid approach). 

Hmm. and before I close out, we love to create collaborative fields in medicine- Cardionephrology, Onconephrology, Diabetonephrology, ICU Nephrology, OB nephrology.... creating niches and making great strides.

Happy Kidney Month

In the NEWS: Cardio-renal syndrome scientific statement by AHA

A scientific statement was just issued on cardio-renal syndrome by the AHA. This is one of the first and comprehensive summary on cardio-nephrology. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Some of the key summaries in the large statement are summarized in table 8 of the freely available statement. The important ones are: Distinguishing true AKI from functional causes of fluctuations in serum creatinine in the context of diuresis for acute decompensated heart failure is critical in ensuring delivery of goal-directed medical therapies; Identifying the factors contributing to diuretic resistance is a key step in optimizing decongestion in cardio-renal syndrome(CRS); Biomarkers of cardiac and kidney injury represent a new dimension in the diagnostic algorithm in evaluating HF with impaired kidney function and offer prognostic value in acute and chronic CRS; High-quality data for goal-directed medical therapy in chronic CRS with moderate to severe decline in kidney function are lacking. In addition, a multidisciplinary approach is required for cardiac device therapies to reduce arrhythmia burden in patients with CHF and CKD. Palliative care is an underused strategy in patients with the dual burden of CHF and advanced CKD. A cardio-nephrology multidisciplinary approach is essential in the joint management of patients with CRS with an emphasis on core outcome measures based on patient and physician priorities. Cross specialty educational programs are extremely important to promote the data on this important topic and also to increase awareness of newer technology. In addition, cross talk within two specialties could breed important decisions to improve patient related outcomes.

Concept Map: Drug Induced TMA

Consult Rounds: Low Urinary Na

Urinary Na concentration is a very useful urinary test that we use in clinical practice to decide the volume status of the patient. It is also very useful in helping decide pre renal vs intrinsic renal disease. 

There are several causes of AKI where urine Na concentration and fractional excretion of Na may be initially low, only to increase later. They are listed below

1.       Radiocontrast agent induced AKI- due to AngII increase and ischemic damage

2.       Sepsis- activation of AngII leads to initial vasoconstriction and low levels of urinary Na

3.       NSAIDs- unopposed vasoconstriction from Ang II

4.       Rhabdomyolysis- mechanism unclear

5.       Acute obstruction( initial phase)- again activation of AngII

6.       Acute GN- cytokines that lead to decrease GFR causing lowering of filtered Na load

7.       Acute rejection- similar to GN

A recent article in CJASN reviews the use of urinary studies in diagnosis of kidney diseases.

HATs off to Nephrology: The various HATs of a nephrologist

As I finished my 2 weeks on consults, I just realized why I love nephrology because it let's me wear various types of HATs

Day 1:- Consult 1: - Minimal Change Disease on kidney biopsy- starting steroids, no secondary cause. Nice GN to start the day ( putting on the GN hat)

Day 2: Consult 3: AKI on CKD in someone with CHF, getting diuresis but serum creatinine rising. Intern says, we stopped diuresis as AKI ensued.  On exam, +JVP, + B lines on our portal lung US exam, Ascites and + LE edema. Dear Intern, please don’t be nephrocentric but continue diuresis as this is renal venous congestion and bingo- 2 days later serum creatinine downtrends. Pre renal success shall we say( putting on the critical care or cardioneph hat)

Day 2: Consult 5: Na of 167, Diabetes Insipidus, bring on the ddavp please!( putting on my electrolyte hat)

Day 3: Consult 3: AKI in someone getting vanco-zosyn combination, rising vancomycin levels and creatinine going from 1mg/dl to 5mg/dl in 3 days. Kidney biopsy confirms ATN/AIN.  That vanco-zosyn combo is becoming lethal to the kidneys. How many drugs can we stop? – NSAIDS, PPIs, Vanco-zosyn. I feel like the medication police!( putting on my AKI hat)

Day 4: Consult 4: Hypomagnesemia severe enough to be admitted 3 times. PPI still on board and FeMg<2%.  Sorry but those PPIs are causing Ulcers for us the Nephrologists!( putting on my electrolyte hat)

Day 5: Consult 5: AKI in a 85 year old with MODs, septic shock and overall poor prognosis. Surprise question asked and dialysis not offered. Palliative care nephrology is important as well. Not every patient is an ideal dialysis candidate( putting on our palliative care nephrology hat)

Day7: Consult 6: Hypercalcemia and an elevated 1,25 vitamin D level- lymphoma, TB or Sarcoid and the only hypercalcemia that responds to steroids!!( putting on the onconephrology hat)

Day 8: Consult 2: AKI with someone with severe AS. Diuresis begins but guiding volume management is a tough decision. Severe AS scares me. Point of care lung US daily assessing for B lines guides management proves to be a great addition to our physical exam.( putting on the ICU nephrology hat)

Day 9: Consult 1: AKI, low platelets, low hemoglobin, rising LDH, down-trending haptoglobin and worsening HTN—bring on the TMA team. From what- virus, systemic disease, complement deficiency, not sure—but oh well onconephrology rocks! ( putting on the onconephrology hat)

Day 10: Consult 1: HTN HTN, HTN severe HTN—adrenal mass, and record high metanephrine levesl- pheochromocytoma in the house!, get the surgeons and endocrine on board( putting on the HTN specialist hat)

Day 11: Consult 2: Hyponatremia 127 but serum osmolality is 290. Hmmmm!! Paraproteins made an appearance and masquerading myeloma- more onconephrology! ( ofcourse this hat comes twice)

Day 12: Consult 3: Acute ESRD, doesn’t want HD--- but would consider acute PD –so urgent start PD done.. The new wave in PD care. Not every patient needs HD, you can in the right environment get urgent start PD and get PD arranged as outpatient- we need to make this mainstream. ( putting on the ESRD hat)

Day 12: Consult 4: AKI and proteinuria in someone with history of SLE. Kidney biopsy shows nodular sclerosis and diabetic nephropathy. No active lupus. Not all kidney biopsies in SLE are lupus nephritis.( putting on the Rheum-Renal hat)

Day 13: Consult 1: AKI, proteinuria - biopsy confirms Post infectious GN, ongoing infection treatment needed. ( putting on the GN hat)

 

Now with the above case listing- wouldn’t you feel so excited. This is why Nephrology is so much fun!! Which other field in medicine allows for so much variety!