We discussed an elderly woman with ESRD who presented with progressive abdominal pain, distention and fevers and was diagnosed with PD (peritoneal dialysis-associated) peritonitis, which was ultimately found to be due to TB!
What is peritoneal dialysis?
In the simplest terms, PD involves the instillation of dialysis fluid into the peritoneum with the goal of achieving solute clearance and ultrafiltration across the peritoneal membrane.
Dialysis fluid ‘dwells’ in the peritoneum while solute and volume move into it; it is then removed via the peritoneal catheter at the end of the dwell
There are three specific infectious complications of PD catheters: 1) PD peritonitis, 2) tunnel infection and 3) exit site infection
The microbiology of PD peritonitis differs somewhat from spontaneous bacterial peritonitis (SBP).
Microbiology of PD peritonitis. Glickman 2017
- NB: unlike SBP, where >250 PMNs or a +culture is necessary for the diagnosis, about 10% of patients with PD peritonitis present without >100 WBCs, so it’s important to have a high suspicion for it
- It’s often a difficult decision as to whether to try to preserve the catheter or to pull it. In general, fungal, mycobacterial and pseudomonal peritonitis necessitate catheter removal.
- You can try to treat through other forms of bacterial PD peritonitis, unless it’s a recurrent or refractory infection
- Recurrent episodes of peritonitis can make the abdomen less hospitable to PD, and can even lead to the development of peritoneal sclerosis, which may lead to small/large bowel obstruction, constipation, malnutrition and death
This patient ultimately had her peritoneal fluid tested for adenosine deaminase (ADA) given the concern for TB. A few quick notes:
- It can be used to distinguish between tuberculous and malignant causes of lymphocytic pleural effusions/ascites, etc.
- Test characteristics vary somewhat between different body sites, but for tuberculous ascites, ADA (particularly values >35) has a ~95% sensitivity and 96% specificity, a positive likelihood ratio of ~16 and a NLR of 0.09!
- Akoh JA. Peritoneal dialysis associated infections: An update on diagnosis and management. World J Nephrol 2012.
Today we discussed a case of acute kidney injury and proteinuria in a patient with well-controlled HIV, who was ultimately diagnosed with IgA nephropathy. It is important to remember that patients with well-controlled HIV have pretty much the same differential for glomerular disease as the general population.
In general, we classify glomerular diseases based on whether all glomeruli (diffuse) or only some (focal) are involved, and within each individual glomerulus whether the entire unit (global) or only part (segmental) is effected.
There are two broad syndromes of glomerular disease: nephrotic syndrome (which is characterized primarily by proteinuria >3.5 g/day) and nephritic syndrome (glomerular inflammation). Urinalysis findings of erythrocyte casts or dysmorphic red cells have a high specificity for glomerular pathology, which can also be suggested by hematuria and proteinuria.
Nephrotic syndrome can be a primary glomerular pathology, or it can be secondary to a systemic disease process (infectious, malignant, or medication-induced). Here is a basic differential for nephrotic syndrome:
- Minimal change disease
- Focal segmental glomerular sclerosis
- Membranous glomerulopathy
- Diabetic nephropathy
Nephritic syndrome can be conceptualized based on mechanism of disease into three categories – pauci-immune (minimal immune cell infiltration), immune complex deposition, and anti-glomerular basement membrane antibody-mediated.
Pauci immune: seen in vasculitis (MPA, GPA, eGPA)
Anti-GBM antibodies: can have pulmonary manifestations (Goodpasture’s syndrome). Inherited collagen IV disorders can also effect renal function.
Immune complex deposition
- IgA nephropathy
- SLE nephritis
- Infection-related glomerulonephritis
- Membranoproliferative glomerulonephritis
In our patient, renal biopsy made the diagnosis of IgA nephropathy!
Today at PPMC we covered one of the basics — microscopic hematuria. We see it ALL the time, we make sure we’ve made the PCP aware in the discharge paperwork — but what does the PCP actually need to DO in follow up? And when should we be forcing more aggressive workup and biopsy?
These were just a few of the great questions asked and answered today. First the PPMC team developed a basic algorithm, and then we moved forward to apply this algorithm to several cases.
We discussed that microscopic hematuria is NEVER normal and our risk stratification really depends on a triage between glomerular sources of bleeding vs. not and then the patients individual risk factors for malignancy. If glomerular in nature, we discussed factors that require an expedited workup with nephrology for biopsy — increasing protein in urine and worsening renal function.
Our first case was a 38 yo with a PMH of recurrent UTI’s and family history of an unknown “renal disease” who was found to have persistent microscopic hematuria. First, using the above algorithm, the team wanted to confirm that she didn’t have a benign reason for microscopic hematuria including her menses or another UTI. Once that testing came back negative we wanted to “start at the top” to determine if the bleeding was glomerular in nature. Her urine demonstrated dysmorphic reds and red cell casts but importantly NO protein and a normal creatinine. Based on this information we reviewed the data behind conservative medical management without biopsy — with the presumptive diagnosis as either thin basement membrane or IgA nephropathy.
Our second case was a 65 yo M recently started on Xarelto for a RLE DVT who was found to have microscopic hematuria after starting anticoagulation. Again, benign causes for bleeding were ruled out and an assessment of his risk factors for malignancy was performed: Age, Smoking status, history of gross hematuria, occupational exposure, h/o cycophosphamide exposure, use of some weight loss/diet preparations with aristolochic acid. This patient was found to have a transitional cell cancer of the bladder.
- Cohen, RA and Brown RS. Microscopic Hematuria. N Engl J Med 2003;348:2330-8.
Thanks to Amy Forrestel for presenting a crazy case today of a 48 year old man who presented with uremia and a presenting Cr of 25, and was ultimately diagnosed with a thrombotic microangiopathy (TMA) secondary to underlying multiple myeloma.
What is a TMA?
TMAs are defined by the presence of arteriolar and capillary vessel wall abnormalities that cause microvascular thrombosis. The hallmark triad of TMA is microangiopathic hemolytic anemia + thrombocytopenia + acute kidney injury. Remember, however that the presence of all three of those features is not specific for TMA, and can be representative of other conditions (see chart below) that manifest similarly. Also keep in mind that many of these disease entities share common pathophysiologic features, and as we were reminded by Dr. Hogan, the biology of TMAs is evolving and far from fully understood.
See this excellent NEJM review about primary TMA syndromes.
- When someone presents with the TMA triad (MAHA+thrombocytopenia+AKI), the first priority is to rule out TTP (caused by ADAMTS13 deficiency), as that requires emergent plasma exchange.
- Send off an ADAMTS13 level; less than ~10% activity suggests TTP (although some malignancies can decrease levels)– but don’t hesitate to empirically start plasma exchange (PEX/PLEX) and adjunctive steroids if you have a high suspicion for TTP and are waiting for ADAMTS13 to result.
In trying to differentiate clinically amongst the primary TMAs, a few pearls:
- Have a high suspicion for Shiga-toxin mediated TMA in patients that present with diarrhea (although other TMAs can present with nonspecific GI sx as well)
- Drug-induced TMA has been linked to quinine (found in tonic water, bitter lemon, antimalarials) most commonly, as well as quetiapine, gemcitabine, and in those that intravenously abuse oxymorphone. Classically, patients who become symptomatic from quinine-induced DITMA will remember the exact moment when they started to feel crummy (see this excellent NEJM case challenge on it which gives a great explanation). See picture below for suspected mechanism.
- TTP tends to have less severe AKI compared to the other TMAs, maybe because it’s a problem with ADAMTS13, and not an intrinsic immune-mediated problem with the renal vascular endothelium
- The risk of post-TMA CKD varies between different causes of TMA (ex: high in quinine-induced TMA, low in Shiga-toxin TMA)
- Complement-mediated TMA (aka atypical HUS) is very rare, and is sort of a diagnosis of exclusion (unless you’re able to send off testing for genetic complement mutations, which only a few places do); once you’ve excluded TTP (using a normal ADAMTS13 level) and the other TMAs by history, you can settle on complement mediated TMA (aka ‘atypical HUS’)
- If complement-mediated TMA is suspected, eculizumab (a monoclonal antibody to C5 which blocks membrane attack complex formation) should be started ASAP.
- Eculizumab caveats: very expensive (~$400K/year), and puts patients at high risk for invasive meningococcal infections (as well as Strep pneumo and H. flu B)
- Random pearl: vasculitis causes glomerulonephritis most commonly; the absence of proteinuria does not rule out vasculitis, and in fact microscopic hematuria on UA is more sensitive for renal vasculitis than the presence of protein
Finally, see the algorithm below for an approach to TMAs
- Legendre et al. Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome. 2013 NEJM. 368 (23) 2169-81.
- Syndromes of TMA. NEJM.
- CDC MMWR. High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine.
- Approach to the patient with suspected TMA. UpToDate.
Today at PPMC we discussed the case of a 63 yo M with nephrogenic DI secondary to hypercalcemia from multiple myeloma — we REALLY covered some ground!
PEARLS for POLYURIA:
1. Use a mechanism driven approach to classifying Polyuria
2. In the office — a UDip and FSG can go a long way!
– Also think about Urine Osm, Serum Osm, BMP, TSH and UDS for intial work up. Don’t forget about a lithium level if appropriate!
3. The mechanism behind hypercalcemia causing polyuria is complicated (1) — but when elevated chronically it can cause a nephrogenic DI!
1. Moeller HB, Rittig S, Fenton RA. Nephrogenic Diabetes Insipidus: Essential Insignts into the Molecular Background and Potential Therapies for Treatment. Endocr Rev. 2013 Apr; 34(2):278-301.
2. Sands JM, Bichet DG. Nephrogenic Diabetes Insipidus. Ann Intern Med. 2006;144:186-194.