Stones (Nephrolithiasis / Urolithiasis)

Infection stones: triple phosphate, magnesium ammonium phosphate, struvite, carbonate apatite

• Randall's Plaque and stone formation

  • Supersaturation of tubular fluid with respect to calcium phosphate and/or calcium oxalate occurs in the kidney tubules at the end of the loop of Henle and beginning of the collecting duct

  • ***

• Low urine volume is a large risk factor for stone formation

  • Normal adult urine is 1.3 L per day

  • Goal for stone formers = drinking enough for 2 L/day of urine

    • Age dependent

• Incidence of nephrolithiasis is increasing

  • 6.3% of men and 4.1% of women affected in 1994

  • 10.6% of men and 7.1% of women in 2012

• Most common urinary chemical abnormalities

  • Hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, high urinary sodium and low urine volume

• Those who experience stones have lower quality of life

• 24 hour urinary testing is underutilized

• 24 hour urine testing

  • Roughly half of renal stones are symptomatic, mostly preventable

  • Prophylactic treatment greatly underutilized

  • Single most critical component of successful preventative management is motivation and discipline of patient

• Collection:

  • What is included in the box? *** see pictures online

  • Instructions available in English in Spanish: ***see pictures available online

  • 24 hours (at least 22 and no more than 26 hours) collected

• Results Report: Bold = falls out of range

  • 1st page: Pediatric Chemistry Data with normalized values (normalized to body weight or body surface area)

    • This gives you pediatric specific norms and is only for patients <18 years

  • 3rd page: 

    • Some redundancy with 1st page

    • Reference ranges are based on adults

    • Normalized values also apply to adults

    • Make sure sample is adequate based on urine volume and 24 hour creatinine

    • Ca, oxalate, citrate levels and treatment options based on adults

• "Analyte variations in consecutive 24-hour urine collections in children" PMID 28739373

  • Significant variability

• Protip: the preservative is an acid and can damage clothing if there is any "splashback"

Gastric bypass, specifically the Roux-en-Y procedure, has been associated with enteric hyperoxaluria and increased risk of calcium oxalate kidney stones.

There are two major sources of oxalate: exogenous food intake and endogenous hepatic metabolism. Enteric hyperoxaluria occurs as a result of fat malabsorption, often caused by inflammatory bowel disease, short gut syndrome, or Roux-en-Y gastric bypass surgery. In healthy intestines, enteric calcium binds to enteric oxalate, chelating it and preventing oxalate from being absorbed into the systemic circulation. When fatty acids and bile acids remain in the intestinal lumen, they bind to calcium, preventing the chelation of enteric oxalate. This unbound oxalate can be absorbed and excreted, leading to hyperoxaluria and stone formation.

Duffey BG, Alanee S, Pedro RN, et al: Hyperoxaluria is a long-term consequence of Roux-en-Y gastric bypass: a 2-year prospective longitudinal study. J Am Coll Surg 211(1): 8‒15, 2010

Duffey BG, Pedro RN, Makhlouf A, et al: Roux-en-Y gastric bypass is associated with early risk factors for development of calcium oxalate nephrolithiasis. J Am Coll Surg 206(6): 1145‒1153, 2008

Upala S, Jaruvongvanich V, Sanguankeo A: Risk of nephrolithiasis, hyperoxaluria, and calcium oxalate supersaturation increased after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis. Surg Obes Relat Dis 12(8): 1513‒1521, 2016

Cochat P, Rumsby G: Primary hyperoxaluria. N Engl J Med 369(7): 649‒658, 2013

• PH is a collection of rare inherited diseases of glyoxylate metabolism leading to increased endogenous oxalate production, leading to kidney stones and nephrocalcinosis

• 80% of patients have the most severe type (type 1), while type 2 and 3 make up about 10% each

• Therapeutic strategies to date:

  • Patients with GFR >30-40

    • Water: 3 liters/m2/day

    • Potassium citrate: 0.5 mmol/kg/day

    • B6 (5-20 mg/kg/d) for some PH1 subtypes (G170R,. F152I, I244T & minor allele)

      • Pyridoxine can restore the function of the enzyme in these patients

      • Glycolate administration leads to glycine appearance, proving pyridoxine sensitivity (B6+)

      • Most patients are B6-

  • Patients with eGFR <30-40

    • eGFR <30: combined liver-kidney tx

    • Dialysis: sequential (1st liver) or combined liver-kidney tx

    • ***

• Transplantation outcomes [Metry 2022]

  • CLKT better than KT in all patients

  • No difference of CLKT-KT in B6+ patients

  • No difference in sequential vs combined

• PH1: peroxisomal defect of AGT

  • Glycolate administration leads to glycine appearance, proving pyridoxine sensitivity

• New RNAi therapies

  • Substrate reduction therapy

    • Prevention of oxalate production by inhibition of precursor

    • Method: RNA interference inhibits protein production

    • 2 products in clinical trials, 1 FDA approved

      • Lumasiran: blockade of glycolate oxidase (GO)

        • [Garrelfs et al., NEJM 2021]

      • Nedosiran: blockade of LDH-A

        • [Hoppe et al., Kidney Int 2021]

  • Safety

    • short term favorable pattern

      • Injection site reaction

      • Potential for Ab induction

      • No liver abnormalities

      • No long term safety data

      • 
        

• Medical expulsive therapy (MET)

  • Distinct from observation alone

  • 4-6 weeks

  • Hydration

    • Not suitable for all kids, e.g., those with developmental delay

  • NSAIDsditrop

  • Flomax

    • Note: not FDA approved for this indication in children, but has been shown to be effective in adults

  • Baseline imaging: KUB and/or KBUS

    • Ultrasound less effective when in the ureter

    • In a pinch, scout image on CT (20% sensitive)

    • Repeat imaging in 6-8 weeks

  • Try to capture the stone

URS - ureteroscopy

• Transurethral

  • Place a wire to delineate the path, and shoot in contrast to evaluate the shape of the kidney

    • Wire placement can result in perforation

  • Must continuously irrigate in order to visualize with the camera

    • if there is a perforation, this need for continuous irrigation can shorten the duration of the case

• Benefits: can directly visualize the stone

• Risks: can injure urethra; can cause silent hydronephrosis in 1% (scarring that is painless, chronic but can result in hydronephrosis)

• Pre-stent and post-stent

  • Pre-stent: may require a stent to be placed to dilate the ureter and make it safe for ureteroscopy

• Decompression with stent or ureterostomy

Extracorporeal shockwave lithotripsy

• Sedation required

• Must be able to localize stone and target it

• Issues:

  • Stone clearance/stent

    • Broken up stone still has to pass

      • Can be problematic in UPJ obstruction, small/narrow ureter; therefore, a stent or percutaneous nephrostomy

  • Hematoma, renal injury

    • Unclear if this causes parenchymal injury

  • Not recommended in fertile females because of the risk of hematoma affecting the ovary

• Machine has to be rented, even at tertiary care center

  • Cases are batched together

PCNL - percutaneous nephrolithotomy

• CT scan

• Going in through the patient's back with the help of interventional radiology

• Often through the lower pole of the kidney

• Improved stone clearance, although has increased morbidity

• Bleeding risk

• Lung/intestinal injury

• Higher risk if anatomy is not normal (e.g., scoliosis)

• Can separate the kidney from the renal pelvis

• For large hard stones in the right patient this is the most efficient and best way to clear their stone burden

AUA has guidelines although they are not closely followed

• Often these do not address major issues, such as UPJ obstruction, reflux, prior surgeries, fertility concerns, developmental delay or other congenital abnormalities

• Asymptomatic and nonobstructing renal stones can be followed with active surveillance

Active surveillance

• For stones:

  • Small enough to pass spontaneously

    • 10 mm in adults

    • Similar cutoff used in kids, given that there is margin of error on the ultrasound measurement

  • Patient is unfit for surgery

• q6 months for 2 years, then sometimes will space to annual follow up

• Initial: stone risk assessment with blood and urine tests

• Follow up: KBUS to assess for stone clearance vs persistence vs increase

Hard stones

• Cystine, brushite, calcium oxalate monohydrate

• ECSL is not effective

• PCNL the best option

• Lasers do not work well

  • Can potentially be done with very long (and potentially multiple) ureteroscopies

  • Some promise for newer laser technologies such as Thulium (Soltive laser), but there are issues with using this in pediatrics because of the heat

• [UpToDate: Kidney stones in children: Epidemiology and risk factors]
• [UpToDate: Kidney stones in children: Clinical features and diagnosis]
• [UpToDate: Kidney stones in children: Prevention of recurrent stones]
  • [UpToDate: Primary hyperoxaluria]
• [UpToDate: Kidney stones in children: Acute management]